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ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
ATP + Akt
ADP + Akt phosphate
ATP + p70S6K
ADP + p70S6K phosphate
-
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
additional information
?
-
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
catalyzed by class I and III, and probably by class II enzymes, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
-
-
phosphatidylinositol-3,4,5-triphosphate is a major product of active PI3K, and recruits Akt/PKB to the plasma membrane and the phosphorylation of Akt occurs
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
p110delta controls a critical checkpoint in peripheral T cell differentiation and clonal expansion
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-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
PI3Kp110delta is the main source of production of 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate following antigen recognition by B cells, T cells and mast cells
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?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
PIP3 acts as a positive regulator of the Src signaling pathway in Xenopus fertilization
-
-
?
ATP + Akt
ADP + Akt phosphate
-
-
-
-
?
ATP + Akt
ADP + Akt phosphate
-
phosphorylation at Ser473
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + phosphatidylinositol
ADP + phosphatidylinositol 3-phosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
-
-
-
?
ATP + phosphatidylinositol 4-phosphate
ADP + phosphatidylinositol 4,5-diphosphate
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
i.e. PIP3, PIP3 recruits protein dependent kinase 1, PDK1, and AKT, also known as protein kinase B, PKB, to the plasma membrane
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
class I PI3Ks
the product allows for the recruitment to the plasma membrane of proteins containing a pleckstrin homology domain
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?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and DNA synthesis
-
-
?
additional information
?
-
-
enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class IA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear
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?
additional information
?
-
-
phosphoinositide 3-kinase and apoptosis
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?
additional information
?
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-
the enzyme is activated and associated to E-cadherin complexes, the assembly is mediated by docking proteins, e.g. beta-catenin, gamma-catenin, and Dlg, and involves c-SRC. Cell-cell adhesion induces c-SRC recruitment and E-cadherin complex assembly as well as activity of PI3K, regulatory and molecular mechanism, overview. PI3K, stimulated by E-cadherin adhesion, activates PKB/Akt
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-
?
additional information
?
-
-
phosphoinositide 3-kinase and DNA synthesis
-
-
?
additional information
?
-
-
enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class IA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear
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?
additional information
?
-
-
phosphoinositide 3-kinase and apoptosis
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?
additional information
?
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-
enzyme can promote proliferation
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?
additional information
?
-
-
phosphoinositide 3-kinase and DNA synthesis
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-
?
additional information
?
-
-
enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class IA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear
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?
additional information
?
-
-
phosphoinositide 3-kinase and apoptosis
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?
additional information
?
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-
enzyme is activated by binding of osteopontin to integrin alphavbeta3
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?
additional information
?
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?
additional information
?
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p110delta does not phosphorylate the p85 adaptor but instead harbors an intrinsic autophosphorylation capacity
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?
additional information
?
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involvement of the enzyme in CD18-mediated adhesion of human neutrophils to fibrinogen
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?
additional information
?
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subunit p101 is responsible for phosphatidylinositol-4,5-bisphosphate substrate selectivity of enzyme gamma isoform by sensitizing p110 gamma toward G-protein beta,gamma-subunits in the presence of phosphatidylinositol-4,5-bisphosphate
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?
additional information
?
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-
PI3K generates phosphatidylinositol 3,4,5 trisphosphate
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?
additional information
?
-
-
the enzyme is activated and associated to E-cadherin complexes, the assembly is mediated by docking proteins, e.g. beta-catenin, gamma-catenin, and Dlg, and involves c-SRC. Cell-cell adhesion induces c-SRC recruitment and E-cadherin complex assembly as well as activity of PI3K, regulatory and molecular mechanism, overview. PI3K, stimulated by E-cadherin adhesion, activates PKB/Akt
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?
additional information
?
-
-
the p85alpha subunit of phosphatidylinositol 3-kinase has GTPase-activating protein activity toward Rab5 and Rab4, small monomeric GTPases important in the regulation of RTK endocytosis, trafficking, and degradation pathways
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?
additional information
?
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regulatory domain p85 interacts with RAS-GTP
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?
additional information
?
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-
the enzyme also catalyzes the reactions of EC 2.7.1.68, 1-phosphatidylinositol-4-phosphate 5-kinase, and EC 2.7.1.67, 1-phosphatidylinositol 4-kinase
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?
additional information
?
-
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the single class 1B catalytic isoform p110gamma binds to either p101 or p84/p87 adaptors, which function to potentiate activation by betagamma-subunits of heterotrimeric GTP-binding proteins which facilitate intracellular signalling from G-protein coupled receptors
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?
additional information
?
-
phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is able to phosphorylate both lipid and protein substrates. In addition to their lipid kinase activity, all members of the class 1 PI3K family also possess intrinsic protein kinase activity
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?
additional information
?
-
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phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is able to phosphorylate both lipid and protein substrates. In addition to their lipid kinase activity, all members of the class 1 PI3K family also possess intrinsic protein kinase activity
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?
additional information
?
-
the enzyme is also active as a serine-dependent protein kinase with Src as substrate and specifically phosphorylating residue Ser70 of Src
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?
additional information
?
-
the enzyme is also active as a serine-dependent protein kinase with Src as substrate and specifically phosphorylating residue Ser70 of Src. No activity with S70A Src mutant
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?
additional information
?
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-
enzyme interacts with active, GTP-bound Ras
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?
additional information
?
-
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enzyme can promote proliferation
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?
additional information
?
-
-
phosphoinositide 3-kinase and DNA synthesis
-
-
?
additional information
?
-
-
enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class IA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and apoptosis
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?
additional information
?
-
-
the adaptor subunits of the class IA enzymes bind phosphorylated Tyr residues, thereby linking the phosphoinositide 3-kinases catalytic subunit to tyr kinase signalling pathways
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?
additional information
?
-
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mechanism of signal down-regulation of insulin receptor substrate mediated by monomeric p85 enzyme regulatory subunit
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?
additional information
?
-
-
p110delta is an important signaling component for efficient axonal elongation in the developing and regenerating nervous system
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?
additional information
?
-
p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN
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?
additional information
?
-
PI3K p110delta contributes to cellular and humoral immunity. PI3K p110delta regulates the diffentiation of peripheral helper T-cells towards the Th1 and Th2 lineages. PI3K p110delta is critical to regulatory T-cell development and function
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?
additional information
?
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PI3K p110delta play a role in the regulation of RAG gene expression and thereby LC allelic/isotype exclusion
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?
additional information
?
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PI3Kgamma plays an important role in neutrophil emigration but not rolling and limited adhesion in postcapillary venules in vivo. The leukocyte but not the endothelial PI3Kgamma is critically involved in the early neutrophil emigration into the inflamed tissues. The delayed neutrophil emigration in response to neutrophil chemokines is independent of the function of PI3Lgamma but is PI3Kdelta dependent
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?
additional information
?
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PI3Kgamma plays an important role in neutrophil emigration but not rolling and limited adhesion in postcapillary venules in vivo. The leukocyte but not the endothelial PI3Kgamma is critically involved in the early neutrophil emigration into the inflamed tissues. The delayed neutrophil emigration in response to neutrophil chemokines is independent of the function of PI3Lgamma but is PI3Kdelta dependent
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?
additional information
?
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role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammation
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?
additional information
?
-
the delayed neutrophil emigration in response to neutrophil chemokines is independent of the function of PI3Lgamma but is PI3Kdelta dependent
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?
additional information
?
-
the delayed neutrophil emigration in response to neutrophil chemokines is independent of the function of PI3Lgamma but is PI3Kdelta dependent
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?
additional information
?
-
-
function of class IA phosphatidylinositol 3-kinases in the pre-T-cell receptor-controlled developmental transition of CD4-/CD8- double-negative to CD4+/CD8+ double-positive thymocytes
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?
additional information
?
-
-
molecular model for the regulation of PI3K signaling by NCoR, a receptor corepressor and regulator of thyroid receptor-activated PI3K signaling
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?
additional information
?
-
-
the single class 1B catalytic isoform p110gamma binds to either p101 or p84/p87 adaptors, which function to potentiate activation by betagamma-subunits of heterotrimeric GTP-binding proteins which facilitate intracellular signalling from G-protein coupled receptors
-
-
?
additional information
?
-
-
a p110alpha/beta-subunit binds to a p85 regulatory subunit, and this heterodimer is recruited to the membrane through the association with phosphotyrosyl proteins, leading to production of phosphatidylinositol 3,4,5-triphosphate, PIP3, followed by activation of downstream signal pathway(s)
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?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ATP + 1-phosphatidyl-1D-myo-inositol
ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate
-
catalyzed by class I and III, and probably by class II enzymes, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
ATP + Akt
ADP + Akt phosphate
-
-
-
-
?
ATP + p70S6K
ADP + p70S6K phosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
additional information
?
-
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-triphosphate
-
-
phosphatidylinositol-3,4,5-triphosphate is a major product of active PI3K, and recruits Akt/PKB to the plasma membrane and the phosphorylation of Akt occurs
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
p110delta controls a critical checkpoint in peripheral T cell differentiation and clonal expansion
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
PI3Kp110delta is the main source of production of 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate following antigen recognition by B cells, T cells and mast cells
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate
-
-
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
catalyzed by class I enzyme, overview. PI3K is part of the plasma membrane E-cadherin signaling complex
-
-
?
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate
-
PIP3 acts as a positive regulator of the Src signaling pathway in Xenopus fertilization
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
i.e. PIP3, PIP3 recruits protein dependent kinase 1, PDK1, and AKT, also known as protein kinase B, PKB, to the plasma membrane
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
class I PI3Ks
the product allows for the recruitment to the plasma membrane of proteins containing a pleckstrin homology domain
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
ATP + phosphatidylinositol-4,5-bisphosphate
ADP + phosphatidylinositol-3,4,5-trisphosphate
-
-
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and DNA synthesis
-
-
?
additional information
?
-
-
enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class IA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and apoptosis
-
-
?
additional information
?
-
-
the enzyme is activated and associated to E-cadherin complexes, the assembly is mediated by docking proteins, e.g. beta-catenin, gamma-catenin, and Dlg, and involves c-SRC. Cell-cell adhesion induces c-SRC recruitment and E-cadherin complex assembly as well as activity of PI3K, regulatory and molecular mechanism, overview. PI3K, stimulated by E-cadherin adhesion, activates PKB/Akt
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and DNA synthesis
-
-
?
additional information
?
-
-
enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class IA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and apoptosis
-
-
?
additional information
?
-
-
enzyme can promote proliferation
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and DNA synthesis
-
-
?
additional information
?
-
-
enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class IA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and apoptosis
-
-
?
additional information
?
-
-
enzyme is activated by binding of osteopontin to integrin alphavbeta3
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
involvement of the enzyme in CD18-mediated adhesion of human neutrophils to fibrinogen
-
-
?
additional information
?
-
subunit p101 is responsible for phosphatidylinositol-4,5-bisphosphate substrate selectivity of enzyme gamma isoform by sensitizing p110 gamma toward G-protein beta,gamma-subunits in the presence of phosphatidylinositol-4,5-bisphosphate
-
-
?
additional information
?
-
-
PI3K generates phosphatidylinositol 3,4,5 trisphosphate
-
-
?
additional information
?
-
-
the enzyme is activated and associated to E-cadherin complexes, the assembly is mediated by docking proteins, e.g. beta-catenin, gamma-catenin, and Dlg, and involves c-SRC. Cell-cell adhesion induces c-SRC recruitment and E-cadherin complex assembly as well as activity of PI3K, regulatory and molecular mechanism, overview. PI3K, stimulated by E-cadherin adhesion, activates PKB/Akt
-
-
?
additional information
?
-
-
the p85alpha subunit of phosphatidylinositol 3-kinase has GTPase-activating protein activity toward Rab5 and Rab4, small monomeric GTPases important in the regulation of RTK endocytosis, trafficking, and degradation pathways
-
-
?
additional information
?
-
phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is able to phosphorylate both lipid and protein substrates. In addition to their lipid kinase activity, all members of the class 1 PI3K family also possess intrinsic protein kinase activity
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is able to phosphorylate both lipid and protein substrates. In addition to their lipid kinase activity, all members of the class 1 PI3K family also possess intrinsic protein kinase activity
-
-
?
additional information
?
-
the enzyme is also active as a serine-dependent protein kinase with Src as substrate and specifically phosphorylating residue Ser70 of Src
-
-
?
additional information
?
-
-
enzyme can promote proliferation
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and DNA synthesis
-
-
?
additional information
?
-
-
enzyme is involved in the synthesis of 3-phosphoinositides. Class I phosphoinositide 3-kinases are further subdivided into class IA and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively. All class I phosphoinositide 3-kinase members also bind to Ras, but the role of this interaction in physiological phosphoinositide 3-kinase signalling is not entirely clear
-
-
?
additional information
?
-
-
phosphoinositide 3-kinase and apoptosis
-
-
?
additional information
?
-
-
the adaptor subunits of the class IA enzymes bind phosphorylated Tyr residues, thereby linking the phosphoinositide 3-kinases catalytic subunit to tyr kinase signalling pathways
-
-
?
additional information
?
-
-
mechanism of signal down-regulation of insulin receptor substrate mediated by monomeric p85 enzyme regulatory subunit
-
-
?
additional information
?
-
-
p110delta is an important signaling component for efficient axonal elongation in the developing and regenerating nervous system
-
-
?
additional information
?
-
p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN
-
-
?
additional information
?
-
PI3K p110delta contributes to cellular and humoral immunity. PI3K p110delta regulates the diffentiation of peripheral helper T-cells towards the Th1 and Th2 lineages. PI3K p110delta is critical to regulatory T-cell development and function
-
-
?
additional information
?
-
PI3K p110delta play a role in the regulation of RAG gene expression and thereby LC allelic/isotype exclusion
-
-
?
additional information
?
-
PI3Kgamma plays an important role in neutrophil emigration but not rolling and limited adhesion in postcapillary venules in vivo. The leukocyte but not the endothelial PI3Kgamma is critically involved in the early neutrophil emigration into the inflamed tissues. The delayed neutrophil emigration in response to neutrophil chemokines is independent of the function of PI3Lgamma but is PI3Kdelta dependent
-
-
?
additional information
?
-
PI3Kgamma plays an important role in neutrophil emigration but not rolling and limited adhesion in postcapillary venules in vivo. The leukocyte but not the endothelial PI3Kgamma is critically involved in the early neutrophil emigration into the inflamed tissues. The delayed neutrophil emigration in response to neutrophil chemokines is independent of the function of PI3Lgamma but is PI3Kdelta dependent
-
-
?
additional information
?
-
role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammation
-
-
?
additional information
?
-
the delayed neutrophil emigration in response to neutrophil chemokines is independent of the function of PI3Lgamma but is PI3Kdelta dependent
-
-
?
additional information
?
-
the delayed neutrophil emigration in response to neutrophil chemokines is independent of the function of PI3Lgamma but is PI3Kdelta dependent
-
-
?
additional information
?
-
-
function of class IA phosphatidylinositol 3-kinases in the pre-T-cell receptor-controlled developmental transition of CD4-/CD8- double-negative to CD4+/CD8+ double-positive thymocytes
-
-
?
additional information
?
-
-
molecular model for the regulation of PI3K signaling by NCoR, a receptor corepressor and regulator of thyroid receptor-activated PI3K signaling
-
-
?
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1-[2-methyl-3-(trifluoromethyl)benzyl]-2-methyl-7-(morpholin-4-yl)-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
-
1-[2-methyl-3-(trifluoromethyl)benzyl]-7-(morpholin-4-yl)-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
-
1-[2-methyl-3-(trifluoromethyl)benzyl]-7-[(2R)-2-methylmorpholin-2-yl]-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
-
1-[4-[(4-methylpiperazin-1-yl)carbonyl]phenyl]-3-[4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d ]pyrimidin-2-yl]phenyl]urea
dual catalytic subunit alpha isoform/mTOR kinase inhibitor, demonstrates inhibition of tumor cell growth in vitro and in vivo and causes suppression of the pathway specific biomarkers in the human MDA-361 cell line
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
-
i.e. LY294002, treatment prevents interleukin-13-induced hyper-responsiveness
2-(6-aminopurin-9-ylmethyl)-5-methyl-3-O-tolyl-3H-quinazolin-4-one
-
i.e.IC87114, selective for isoform p110delta. Treatment prevents interleukin-13-induced hyper-responsiveness
2-(difluoromethyl)-1-[4,6-di-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole
lead compound for structure-activity study
2-(methylsulfanyl)-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
-
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(2methylmorpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
-
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
-
2-[(6-amino-9H-purin-9-yl)methyl]-5-methyl-3-(2-methylphenyl)-4(3H)-quinazolinone
-
i.e. IC87114, selectively inhibits isoform p110delta
3-(2-morpholino-6-(2-(pyridin-4-yl)ethylamino)pyrimidin-4-yl)phenol
-
3-(2-morpholino-6-(pyridin-2-ylmethoxy)pyrimidin-4-yl)phenol
-
3-(4-morpholino-6-(pyridin-2-yl)pyrimidin-2-yl)phenol
-
3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one
i.e. CAL-101, highly selective and small molecule inhibitor of isoform PI3Kdelta. Inhibitor blocks constitutive phosphatidylinositol-3-kinase signaling, resulting in decreased phosphorylation of Akt and other downstream effectors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis
3-[4-(4-morpholinyl)thieno(3,2-d)pyrimidin-2-yl]-phenol
-
a p110 PI3K isoform selective inhibitor
3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol
among the compounds tested, treatment with 3-[4-(morpholin-4-yl)thieno[3,2-d]pyrimidin-2-yl]phenol or 3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol leads to the most efficient inhibition
3-[4-(morpholin-4-yl)thieno[3,2-d]pyrimidin-2-yl]phenol
among the compounds tested, treatment with 3-[4-(morpholin-4-yl)thieno[3,2-d]pyrimidin-2-yl]phenol or 3-[4-(morpholin-4-yl)pyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl]phenol leads to the most efficient inhibition
4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
not inhibitory to serine/threonine kinase mTOR; not inhibitory to serine/threonine kinase mTOR
4-[2-[(6-methoxypyridin-3-yl)amino]-5-phenylpyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
not inhibitory to serine/threonine kinase mTOR; not inhibitory to serine/threonine kinase mTOR
4-[4-(morpholin-4-yl)-5a,6-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl]phenol
4-[5-(3,6-dihydro-2H-pyran-4-yl)-2-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
not inhibitory to serine/threonine kinase mTOR; not inhibitory to serine/threonine kinase mTOR
5-[2,2-difluoro-benzo(1,3)-dioxol-5-ylmethylene]-thiazolidine-2,4-dione
-
a p110 PI3K isoform selective inhibitor
6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
inhibitory against all three class Ia PI 3-kinase enzymes, i.e. p110alpha, p110beta, and p110delta, and also displays significant potency against two mutant forms of the p110alpha isoform, H1047R and E545K. In an in vivo U87MG human glioblastoma tumor xenograftmodel in Rag1-/- mice, and at a dose of 50mg/kg given by intraperitoneal injection it dramatically reduces cancer growth by 81% compared to untreated controls
7-methyl-2-(4-morpholinyl)-9-[1-(phenylamino)ethyl]-4H-pyrido[1,2-a]pyrimidin-4-one
-
i.e. TGX221, selectively inhibits isoform p110beta. Compound decreases secretion of vascular endothelial growth factor and interleukin-6 in nonasthmatic airway smooth muscle cells and lung fibroblasts
AS604850
PI3Kgamma inhibitor 2
Baicalin
-
10 microM, 35.5% inhibition of isoform PI3Kalpha
BYL719
a p110alpha-specific inhibitor, BYL719 fails to display selective growth inhibition in p110alphahigh cells
-
CAL-101
-
a specific inhibitor of the PI3Kdelta isoform
CapG
-
nuclear actin-regulatory protein
-
GSK2636771
a p110beta-specific inhibitor
-
HS173
a p110alpha-specific inhibitor
-
luteolin
-
1 microM, 75.8% inhibition of isoform PI3Kalpha
MLN1117
a p110alpha-specific inhibitor
-
myricetin
-
1 microM, almost complete inhibition of isoform PI3Kalpha
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylidene]-N,2-dimethyl-5-nitrobenzenesulfonohydrazide
-
i.e.PIK75, selectively inhibits isoform p110alpha. In cells stimulated with transforming growth factor-beta and/or 10% fetal bovine serum, compound attenuates transforming growth factor-induced fibronectin deposition in all cell types tested and decreases secretion of vascular endothelial growth factor and interleukin-6 in nonasthmatic airway smooth muscle cells and lung fibroblasts. Compound decreases cell survival in transforming growth factor-stimulated asthmatic, but not nonasthmatic, airway smooth muscle cells
N-[2-(dimethylamino)ethyl]-N-methyl-4-[([4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d ]pyrimidin-2-yl]phenyl]carbamoyl)amino]benzamide
dual catalytic subunit alpha isoform/mTOR kinase inhibitor, demonstrates inhibition of tumor cell growth in vitro and in vivo and causes suppression of the pathway specific biomarkers in the human MDA-361 cell line. Good in vivo efficacy in the MDA361 human breast tumor xenograft model
PI103
-
suppressing phosphatidylinositol 3-kinase activity by inhibitors LY294002 and PI103 selectively reduces both the mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator PGC-1beta but not PGC-1alpha. Reducing PGC-1b expression also leads to reduced mRNA expression levels of uncoupling protein 1, 2 and superoxide dismutase 2. Correspondingly, mitochondrial membrane potential and reactive oxygen species levels are increased
PIK75
p110alpha inhibitor PIK75 shows a strong cytotoxicity to all glioblastoma cell lines tested
quercetagetin
-
1 microM, almost complete inhibition of isoform PI3Kalpha
TGX-221-R
R-enantiomer of inhibitor TGX-221, 100fold more potent as a PI3K-beta inhibitor than the S-enantiomer
YM024
a p110alpha-selective PI3K inhibitor
-
ZSTK474
-
a phosphatidylinositol 3-kinase inhibitor, inhibited phosphorylation of Ser65, Thr70 and Thr37/46 in 4E-BP1 by PI3K. Identification of the ZSTK474-sensitive phosphoproteins in A-549 cells, overview
[(4-[2-[(3-hydroxyphenyl)amino]-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl)amino]acetonitrile
lead compound for structure-based design of inhibitors, dual inhibitor of phosphatidylinositol 3-kinase and serine/threonine kinase mTOR; lead compound for structure-based design of inhibitors, dual inhibitor of phosphatidylinositol 3-kinase and serine/threonine kinase mTOR
[3-[4-morpholin-4-yl-7-(pyrrolidin-1-ylmethyl)-5H-pyrrolo-[3,2-d ]pyrimidin-2-yl]phenyl]methanol
selective for catalytic subunit alpha isoform
3-Methyladenine
-
treatment in full medium for a prolonged period of time leads to marked increases of the autophagic markers in cells. The increase of autophagic markers is the result of enhanced autophagic flux. The autophagy promotion activity is due to its differential temporal effects on class I and class III PI3K enzymes. 3-Methyladenine blocks class I PI3K persistently, whereas its suppressive effect on class III PI3K is transient. Treatment with 3-methyladenine in full medium significantly reduces the level of phosphatidylinositol 3-phosphate, the product of class III PI3K, at early time points, but almost completely blocks the product of phosphatidylinositol 3,4,5-trisphosphate up to 9 h
3-Methyladenine
-
treatment in full medium for a prolonged period of time leads to marked increases of the autophagic markers in cells. The increase of autophagic markers is the result of enhanced autophagic flux. The autophagy promotion activity is due to its differential temporal effects on class I and class III PI3K enzymes. 3-Methyladenine blocks class I PI3K persistently, whereas its suppressive effect on class III PI3K is transient. Treatment with 3-methyladenine in full medium significantly reduces the level of phosphatidylinositol 3-phosphate, the product of class III PI3K, at early time points, but almost completely blocks the product of phosphatidylinositol 3,4,5-trisphosphate up to 9 h
4-[4-(morpholin-4-yl)-5a,6-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl]phenol
-
i.e. PI103. Inhibitory to phosphatidylinositol 3-kinases, TORC1 and DNA protein kinase. PI103 potently inhibits proliferation and invasion of a wide variety of human cancer cells in vitro and shows biomarker modulation consistent with inhibition of phosphatidylinositide 3-kinase signaling
4-[4-(morpholin-4-yl)-5a,6-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl]phenol
-
i.e. PI-103. In human leukemic cell lines and in primary blast cells from acute myelogenous leukemia patients, PI-103 inhibits constitutive and growth factor-induced PI3K/Akt and mTORC1 activation. PI-103 is essentially cytostatic for cell lines and induces cell cycle arrest in the G1 phase. In blast cells, PI-103 inhibits leukemic proliferation, the clonogenicity of leukemic progenitors and induces mitochondrial apoptosis. PI-103 has additive proapoptotic effects with etoposide in blast cells and in immature leukemic cells. PI-103 does not induce apoptosis in normal CD34þ cells and has moderate effects on their clonogenic and proliferative properties
AS605240
PI3Kgamma inhibitor 1
AS605240
-
a specific PI3Kgamma inhibitor, significantly delays lethality in Plasmodium berghei-infected wild-type micer
IC-87114
p110delta-specific small molecule inhibitor
IC-87114
p110delta-specific small molecule inhibitor
IC87114
-
a specific inhibitor of the PI3Kdelta isoform, inhibits AML proliferation and augments the effects of a topoisomerase 2 inhibitor
IC87114
-
a selective PI3Kdelta inhibitor
idelalisib
5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]quinazolin-4(3H)-one, a PI3Kdelta inhibitor used to treat hematological malignancies. The inhibitor idelalisib is selective, noncovalent, reversible, and ATP-competitive. The compound binds reversibly and noncovalently to the p110delta subunit of the kinase, analysis of binding interactions that confer the potency and selectivity of idelalisib, overview. Idelalisib is a propeller-shaped inhibitor
idelalisib
CAL-101, a p110delta inhibitor
LY294002
-
-
LY294002
-
a PI3K-specific inhibitor
LY294002
-
specific inhibitor
LY294002
-
a quercetin analogue
LY294002
-
suppressing phosphatidylinositol 3-kinase activity by inhibitors LY294002 and PI103 selectively reduces both the mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator PGC-1beta but not PGC-1alpha. Reducing PGC-1b expression also leads to reduced mRNA expression levels of uncoupling protein 1, 2 and superoxide dismutase 2. Correspondingly, mitochondrial membrane potential and reactive oxygen species levels are increased
LY294002
-
a PI3K-specific inhibitor
LY294002
-
a specific #PI3K inhibitor
LY294002
-
inhibits sperm-induced activation of the tyrosine kinase Src and a transient increase in the intracellular concentration of Ca2+ at fertilization. LY294002 also has an inhibitory effect on the Ca2+-dependent breakdown of the Mos protein kinase and cyclin B2 as well as dephosphorylation of mitogenactivated protein kinase
PI-103
-
a dual PI3K/mTOR inhibitor and a small synthetic molecule of the pyridofuropyrimidine class. PI-103 induces caspase activation and is cytotoxic to all T-cell acute lymphoblastic leukemia cell lines affecting PI3K/Akt/mTOR signaling, mechanism, overview
PI-103
-
shows increased efficacy in inhibiting the growth of glioma cells due to its activity against both the class I PI3Ks and the PIK family member mTor
PIK-75
p110alpha-specific small molecule inhibitor
PIK-75
a p110alpha-selective PI3K inhibitor
PIK-75
p110alpha-specific small molecule inhibitor; p110alpha-specific small molecule inhibitor
PIK-75
p110alpha-specific small molecule inhibitor
PX-866
-
irreversible PI3K inhibitor, shows selectivity for the alpha, delta, and gamma class I PI3K isoforms, inhibits the beta isoform at higher concentrations, and shows decreased selectivity for mTor
PX-866
-
a PI3K inhibitor, inhibits also the oncogenic K-ras-induced bronchioalveolar stem cell accumulation and tumor growth in vivo
quercetin
-
1 microM, 54.1% inhibition of isoform PI3Kalpha
quercetin
-
from red wine extract, quercetin and red wine polyphenol extract inhibit the phosphorylation of Akt in vivo and show inhibitory effects on TNF-alpha-induced upregulation of MMP-9 and on the migratory phenotype of JB6 P+ mouse epidermal, mediated by suppression of the phosphorylation of Akt and the transactivation of activator protein-1 and nuclear factor-kappaB. Red wine extract and quercetin suppress TNF-alpha-induced PI3K activity by binding specifically to PI3K
TGX-221
-
a p110 PI3K isoform selective inhibitor
TGX-221
p110beta-specific small molecule inhibitor
TGX-221
a p110beta-specific inhibitor
TGX-221
p110beta-specific small molecule inhibitor
Wortmannin
-
-
Wortmannin
in nanomolar range
Wortmannin
-
member of a class of steroidal furanoids, shows equally potent activity against all the class I PI3K enzymes, has antiproliferative effect
Wortmannin
-
treatment with wortmannin results in sustained reduction of phosphatidylinositol 3-phosphate and a transient effect on production of phosphatidylinositol 3,4,5-trisphosphate with recovery after 9 h
Wortmannin
a PI3K inhibitor
Wortmannin
-
treatment prevents interleukin-13-induced hyper-responsiveness
Wortmannin
-
treatment with wortmannin results in sustained reduction of phosphatidylinositol 3-phosphate and a transient effect on production of phosphatidylinositol 3,4,5-trisphosphate with recovery after 9 h
XL147
-
targets only the class I PI3Ks
additional information
-
inhibition of PIK3CA induces apoptosis in mantle cell lymphoma cell lines
-
additional information
-
cyclic stretch causes a sustained decrease in activation of PI3-kinase and inhibits wound healing
-
additional information
-
pan-PI3K inhibition and inhibition of only PI3Kdelta results in attenuated vascular leakage, tissue eosinophilia, airway mucus production, and AHR as well as release of cytokines, chemokines and adhesion molecules
-
additional information
-
inhibitory activity of eighteen flavonoids and deduction of their structure-activity relationships. The number of hydroxyl groups in the A and B rings might promote the activity, while loss of C2-C3 double bond might reduce the activity. The results indicate that the flavonoids seem to exhibit more potent activity on PI3Kalpha and delta isoforms compared with that on PI3Kbeta and gamma isoforms
-
additional information
in its resting state, PI3Kapha is autoinhibited by the interaction of a loop of the helical domain of p110alpha with a groove in the nSH2 domain of p85alpha. Despite this inhibition, the enzyme has a significant basal activity
-
additional information
blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1
-
additional information
-
blockade of PI3K lipid signaling by expression of the pleckstrin homology of Akt1
-
additional information
-
a combination of INPP4B overexpression and rucaparib blocks the PI3K/AKT signal pathway
-
additional information
p110alpha-specific inhibitors (PIK75, BYL719, MLN1117, and HS173) are significantly toxic to astrocytes. The p110beta inhibitor TGX-221 and GSK2636771 mitigate the proliferation of p110betahigh U87MG and SF295 cells while having no effect on p110betalow A172 and LN229 cells
-
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0.000001
1-[2-methyl-3-(trifluoromethyl)benzyl]-2-methyl-7-(morpholin-4-yl)-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.000003
1-[2-methyl-3-(trifluoromethyl)benzyl]-7-(morpholin-4-yl)-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.000001
1-[2-methyl-3-(trifluoromethyl)benzyl]-7-[(2R)-2-methylmorpholin-2-yl]-6,7-dihydroimidazo[1,2-a]pyrimidin-5(1H)-one
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0000024
1-[4-[(4-methylpiperazin-1-yl)carbonyl]phenyl]-3-[4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d ]pyrimidin-2-yl]phenyl]urea
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0000004 - 0.0013
2-(methylsulfanyl)-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
0.0000003 - 0.00032
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(2methylmorpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
0.0000006 - 0.00079
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
0.00014 - 0.0016
3-(2-morpholino-6-(2-(pyridin-4-yl)ethylamino)pyrimidin-4-yl)phenol
0.00011 - 0.00073
3-(2-morpholino-6-(pyridin-2-ylmethoxy)pyrimidin-4-yl)phenol
0.000044 - 0.0001
3-(4-morpholino-6-(pyridin-2-yl)pyrimidin-2-yl)phenol
0.0000025 - 0.00082
3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one
0.00058
3-[4-(4-morpholinyl)thieno(3,2-d)pyrimidin-2-yl]-phenol
Homo sapiens
-
versus p110alpha PI3K
0.000002 - 0.000009
4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
0.000001 - 0.000007
4-[2-[(6-methoxypyridin-3-yl)amino]-5-phenylpyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
0.000002 - 0.000005
4-[5-(3,6-dihydro-2H-pyran-4-yl)-2-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
0.00025
5-[2,2-difluoro-benzo(1,3)-dioxol-5-ylmethylene]-thiazolidine-2,4-dione
Homo sapiens
-
about, versus p110gamma PI3K
0.00000022 - 0.0000014
6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
0.008
LY294002
Homo sapiens
-
inhibition of bacterial entry into macrophages
0.0000009
N-[2-(dimethylamino)ethyl]-N-methyl-4-[([4-[4-morpholin-4-yl-7-(2,2,2-trifluoroethyl)-7H-pyrrolo[2,3-d ]pyrimidin-2-yl]phenyl]carbamoyl)amino]benzamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.00004
TGX-221
Homo sapiens
-
about, versus p110beta PI3K
0.000006
TGX-221-R
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.0000025
Wortmannin
Homo sapiens
-
inhibition of bacterial entry into macrophages
0.000052 - 0.00035
[(4-[2-[(3-hydroxyphenyl)amino]-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl)amino]acetonitrile
0.000021
[3-[4-morpholin-4-yl-7-(pyrrolidin-1-ylmethyl)-5H-pyrrolo-[3,2-d ]pyrimidin-2-yl]phenyl]methanol
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
additional information
additional information
Homo sapiens
-
IC50 value of inhibitor 4-[4-(morpholin-4-yl)-5a,6-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl]phenol is 2 nmol/l against recombinant isoform p110alpha, 3 nmol/l against recombinant isoform p110beta, 3 nmol/l against recombinant isoform p110delta, 15 nmol/l against recombinant isoform p110agamma
-
0.0000004
2-(methylsulfanyl)-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
beta isoform, pH not specified in the publication, temperature not specified in the publication
0.000025
2-(methylsulfanyl)-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
delta isoform, pH not specified in the publication, temperature not specified in the publication
0.00032
2-(methylsulfanyl)-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
alpha isoform, pH not specified in the publication, temperature not specified in the publication
0.0013
2-(methylsulfanyl)-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
gamma isoform, pH not specified in the publication, temperature not specified in the publication
0.0000003
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(2methylmorpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
beta isoform, pH not specified in the publication, temperature not specified in the publication
0.000004
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(2methylmorpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
delta isoform, pH not specified in the publication, temperature not specified in the publication
0.00006
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(2methylmorpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
gamma isoform, pH not specified in the publication, temperature not specified in the publication
0.00032
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(2methylmorpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
alpha isoform, pH not specified in the publication, temperature not specified in the publication
0.0000006
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
beta isoform, pH not specified in the publication, temperature not specified in the publication
0.00002
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
delta isoform, pH not specified in the publication, temperature not specified in the publication
0.00063
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
alpha isoform, pH not specified in the publication, temperature not specified in the publication
0.00079
2-methyl-3-[2-methyl-3-(trifluoromethyl)benzyl]-5-(morpholin-4-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one
Homo sapiens
gamma isoform, pH not specified in the publication, temperature not specified in the publication
0.00014
3-(2-morpholino-6-(2-(pyridin-4-yl)ethylamino)pyrimidin-4-yl)phenol
Homo sapiens
isoform p110alpha, pH 7.4, 22°C
0.00074
3-(2-morpholino-6-(2-(pyridin-4-yl)ethylamino)pyrimidin-4-yl)phenol
Homo sapiens
isoform p110gamma, pH 7.4, 22°C
0.0016
3-(2-morpholino-6-(2-(pyridin-4-yl)ethylamino)pyrimidin-4-yl)phenol
Homo sapiens
isoform p110beta, pH 7.4, 22°C
0.00011
3-(2-morpholino-6-(pyridin-2-ylmethoxy)pyrimidin-4-yl)phenol
Homo sapiens
isoform p110alpha, pH 7.4, 22°C
0.00037
3-(2-morpholino-6-(pyridin-2-ylmethoxy)pyrimidin-4-yl)phenol
Homo sapiens
isoform p110beta, pH 7.4, 22°C
0.00073
3-(2-morpholino-6-(pyridin-2-ylmethoxy)pyrimidin-4-yl)phenol
Homo sapiens
isoform p110gamma, pH 7.4, 22°C
0.000044
3-(4-morpholino-6-(pyridin-2-yl)pyrimidin-2-yl)phenol
Homo sapiens
isoform p110gamma, pH 7.4, 22°C
0.000062
3-(4-morpholino-6-(pyridin-2-yl)pyrimidin-2-yl)phenol
Homo sapiens
isoform p110alpha, pH 7.4, 22°C
0.0001
3-(4-morpholino-6-(pyridin-2-yl)pyrimidin-2-yl)phenol
Homo sapiens
isoform p110beta, pH 7.4, 22°C
0.0000025
3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one
Homo sapiens
isoform PI3Kdelta, pH not specified in the publication, temperature not specified in the publication
0.000089
3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one
Homo sapiens
isoform PI3Kgamma, pH not specified in the publication, temperature not specified in the publication
0.000565
3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one
Homo sapiens
isoform PI3Kbeta, pH not specified in the publication, temperature not specified in the publication
0.00082
3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one
Homo sapiens
isoform PI3Kalpha, pH not specified in the publication, temperature not specified in the publication
0.000002
4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform delta, pH not specified in the publication, temperature not specified in the publication
0.000004
4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform gamma, pH not specified in the publication, temperature not specified in the publication
0.000005
4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform beta, pH not specified in the publication, temperature not specified in the publication
0.000009
4-(2-((6-methoxypyridin-3-yl)amino)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform alpha, pH not specified in the publication, temperature not specified in the publication
0.000001
4-[2-[(6-methoxypyridin-3-yl)amino]-5-phenylpyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform delta, pH not specified in the publication, temperature not specified in the publication
0.000002
4-[2-[(6-methoxypyridin-3-yl)amino]-5-phenylpyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform beta, pH not specified in the publication, temperature not specified in the publication
0.000003
4-[2-[(6-methoxypyridin-3-yl)amino]-5-phenylpyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform alpha, pH not specified in the publication, temperature not specified in the publication
0.000007
4-[2-[(6-methoxypyridin-3-yl)amino]-5-phenylpyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform gamma, pH not specified in the publication, temperature not specified in the publication
0.000002
4-[5-(3,6-dihydro-2H-pyran-4-yl)-2-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform delta, pH not specified in the publication, temperature not specified in the publication
0.000002
4-[5-(3,6-dihydro-2H-pyran-4-yl)-2-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform gamma, pH not specified in the publication, temperature not specified in the publication
0.000003
4-[5-(3,6-dihydro-2H-pyran-4-yl)-2-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform beta, pH not specified in the publication, temperature not specified in the publication
0.000005
4-[5-(3,6-dihydro-2H-pyran-4-yl)-2-[(6-methoxypyridin-3-yl)amino]pyridin-3-yl]-6-methyl-1,3,5-triazin-2-amine
Homo sapiens
isoform alpha, pH not specified in the publication, temperature not specified in the publication
0.00000022
6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
Homo sapiens
isoform p110alpha, pH not specified in the publication, temperature not specified in the publication
0.00000038
6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
Homo sapiens
isoform p110delta, pH not specified in the publication, temperature not specified in the publication
0.0000014
6-amino-2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-4-methoxy-1H-benzimidazole
Homo sapiens
isoform p110beta, pH not specified in the publication, temperature not specified in the publication
0.000052
[(4-[2-[(3-hydroxyphenyl)amino]-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl)amino]acetonitrile
Homo sapiens
isoform delta, pH not specified in the publication, temperature not specified in the publication
0.00012
[(4-[2-[(3-hydroxyphenyl)amino]-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl)amino]acetonitrile
Homo sapiens
isoform gamma, pH not specified in the publication, temperature not specified in the publication
0.00019
[(4-[2-[(3-hydroxyphenyl)amino]-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl)amino]acetonitrile
Homo sapiens
isoform beta, pH not specified in the publication, temperature not specified in the publication
0.00035
[(4-[2-[(3-hydroxyphenyl)amino]-1H-benzimidazol-1-yl]-1,3,5-triazin-2-yl)amino]acetonitrile
Homo sapiens
isoform alpha, pH not specified in the publication, temperature not specified in the publication
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evolution
class 1 phosphoinositide 3-kinases are heterodimers consisting of an 85 kDa regulatory/adapter subunit (p85) coupled to a 110 kDa catalytic subunit (p110) with both subunits possessing several isoforms. The class I enzymes are further subdivided into two subclasses: class Ia and class Ib. The class 1a phosphoinositol 3-kinases (p110alpha, p110beta and p110delta) signal downstream of tyrosine kinases, while the single class Ib phosphoinositol 3-kinase (p110gamma) operates downstream of heterotrimeric GPCRs (G-protein-coupled receptors)
evolution
class I PI3K genes control the activity of PI3K/AKT signaling and are often genetically altered in glioblastoma. Class II PI3K genes are implicated in regulating angiogenesis and cilium function. Class III PI3K genes are primarily involved in the regulation of autophagy. Compared to other class IA PI3K isoforms, PIK3CB is the only PI3K catalytic subunit that showed a strong association with recurrence rate, risk, and prognosis
malfunction
-
aberrant activation of the phosphatidylinositol 3-kinase pathway is involved in a wide range of cancers. Mutations in subunit isoform p110alpha are involved in development of bladder cancer, and are also common in the benign skin lesions seborrheic keratosis and epidermal nevi
malfunction
-
aberrant PI3K signaling has been found to play an important role in multiple aspects of tumorgenesis including uncontrolled proliferation, resistance to apoptosis, angiogenesis and metastatic capability. The PI3Kbeta isoform is implicated as necessary for transformation induced by the loss or inactivation of the PTEN tumor suppressor both in vitro and in vivo
malfunction
-
binding of thyroid receptor to p85alpha activates PI3K/AKT signaling promoting thyroid carcinogenesis by increasing cell proliferation and tumor metastasis
malfunction
-
chronic blockade of phosphatidylinositol 3-kinase in the nucleus tractus solitarii is prohypertensive in the spontaneously hypertensive rat
malfunction
-
constitutively activated phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin, mTOR, signaling is a common feature of T-cell acute lymphoblastic leukemia, where it strongly influences growth and survival
malfunction
-
deregulated signaling through phosphatidylinositol 3'-kinase pathway is common in many types of malignancies, including mantle cell lymphoma. PI3K catalytic subunit alpha gene amplification contributes to the pathogenesis of mantle cell lymphoma. Inhibition of PIK3CA induces apoptosis in mantle cell lymphoma cell lines
malfunction
-
individual class I PI3K isoforms are strongly linked with the regulation of oncogenes and tumorigenesis. PI3Ka is upregulated and/or mutated in a variety of carcinomas, and in particular lung tumours, and is associated with an elevation in activation and signalling of the serine-threonine kinase Akt, overview
malfunction
-
inhibition of PI3-kinase or expression of a dominant negative form of PI3-kinase cause inhibition of airway epithelial cell wound closure
malfunction
-
PI3K is involved in non-small cell lung cancer and is PI3K is required for malignant progression in lung cancer, regulation mechanisms, overview
malfunction
-
PI3K signalling is involved in development of respiratory diseases, such as asthma and cystic fibrosis, and lung cancer, detailed overview. Inhibition of PI3Kdelta and gamma may provide a beneficial therapeutic strategy for the reduction of Th1/Th2 and Tc1 cells in respiratory disease. Individual class I PI3K isoforms are strongly linked with the regulation of oncogenes and tumorigenesis. PI3Ka is upregulated and/or mutated in a variety of carcinomas, and in particular lung tumours, and is associated with an elevation in activation and signalling of the serine-threonine kinase Akt, overview
malfunction
-
PI3Ks constitute important regulators of various signaling pathways with relevance in cancer. Activation of PI3K by membrane localization of subunit p110alpha predisposes mammary glands to neoplastic transformation
malfunction
-
PI3Ks constitute important regulators of various signaling pathways with relevance in cancer. Enhanced activation of p110A, the catalytic subunit of PI3K, woccurs in a high proportion of many human tumor types. Activation of PI3K by membrane localization of subunit p110alpha predisposes mammary glands to neoplastic transformation. Perturbation of the interaction of the CDK4/Rb/E2F cascade and the PI3K signaling occurs in many human cancers
malfunction
-
suppression of the PI3K catalytic subunit p110alpha inhibits the growth of ovarian cancer cells in vitro and in vivo, inhibiting decreased cell viability and induced cell apoptosis
malfunction
isoproterenol-induced EGFR transactivation is abolished in PI3Kgamma null mutants or through enzyme inhibition by wortmannin or LY-294002
malfunction
p110delta deficiency did not affect vascular remodeling in vivo
malfunction
p110delta deficiency did not affect vascular remodeling in vivo
malfunction
-
Plasmodium berghei ANKA-infected PI3Kgamm knockout mice show greater survival despite similar parasitemia levels in comparison with infected wild-type mice. Histopathological analysis demonstrates reduced hemorrhage, leukocyte accumulation and vascular obstruction in the brain of infected PI3Kgamma null mice. PI3Kgamma deficiency also causes lower microglial activation and T cell cytotoxicity in the brain. On day 6 post-infection, CD3+/CD8+ T cells are significantly reduced in the brain of infected PI3Kgamma null mice when compared to infected wild-type mice and expression of CD44 in CD8+ T cell population in the brain tissue and levels of phospho-IkappaB-alpha in the whole brain are also markedly lower in infected PI3Kgamma null mice, phenotype, overview
malfunction
the PI3Kalpha signaling pathway is activated in numerous cancers, where the PI3KCA gene, which encodes for the p110alpha PI3Kalpha subunit, is mutated. Oncogenic mutations that are far from the catalytic site and increase the enzymatic affinity, destabilize the p110alpha/p85alpha dimer. By affecting the dynamics of the protein, these mutations favor the conformations that reduce the autoinhibitory effect of the p85alpha nSH2 domain. Molecular dynamics simulations suggest that all the tumor-associated mutations effectively weaken the interactions between the p110alpha and the p85alpha subunits by disrupting key stabilizing interactions
malfunction
-
a combination of INPP4B overexpression and rucaparib blocks the PI3K/AKT signal pathway
malfunction
a patient with a somatic gain of function PIK3CA-mutation (a pathogenic heterozygous missense mutation in PIK3CA) shows extensive multisystem overgrowth, clinical diversity of the PIK3CA-related overgrowth spectrum (PROS), phenotype, overview. The patient has overlapping features of congenital lipomatous overgrowth vascular malformations epidermal nevi and skeletal abnormalities (CLOVES) syndrome and megalencephaly-capillary malformation polymicrogyria (MCAP) syndrome
malfunction
PIK3CA subunit mutations have no correlation with recurrence rate of glioblastoma. Knockdown of PIK3CA/p110alpha in a panel of glioblastoma cell lines shows that loss of PIK3CA/p110alpha fails to both inactivate AKT and block the survival of A172, U87MG, SF295, and U251 glioblastoma cells. Compared to PIK3CA, oncogenic PIK3CB mutations are rare in glioblastoma. Knockdown or inhibitors of PIK3CD/p110delta fails to inhibit AKT and cell viability
malfunction
treatment of cells with the PI3K inhibitor wortmannin, significantly attenuates GLUT4 exocytosis. Cellular deficiency of insulin signaling machineries dampens the expression of the insulin signaling proteins and obliterates downstream signaling mediated through the PI3K pathway
malfunction
-
Plasmodium berghei ANKA-infected PI3Kgamm knockout mice show greater survival despite similar parasitemia levels in comparison with infected wild-type mice. Histopathological analysis demonstrates reduced hemorrhage, leukocyte accumulation and vascular obstruction in the brain of infected PI3Kgamma null mice. PI3Kgamma deficiency also causes lower microglial activation and T cell cytotoxicity in the brain. On day 6 post-infection, CD3+/CD8+ T cells are significantly reduced in the brain of infected PI3Kgamma null mice when compared to infected wild-type mice and expression of CD44 in CD8+ T cell population in the brain tissue and levels of phospho-IkappaB-alpha in the whole brain are also markedly lower in infected PI3Kgamma null mice, phenotype, overview
-
metabolism
-
PI3K is part of the PI3K signaling pathway that is upregulated in cancer
metabolism
-
PI3K/Akt/mTOR signaling, overview
metabolism
-
Rac1 regulates peptidoglycan-induced nuclear factor-kappaB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages by activating the phosphatidylinositol 3-kinase/Akt pathway
metabolism
-
the phosphatidylinositol 3-kinase pathway is a critical signal transduction pathway that regulatesmultiple cellular functions, class IA PI3K signalling pathway, overview
metabolism
-
the signaling cascade involving the enzyme is known as the PI3K/Akt/mTor axis
metabolism
-
WASP activation downstream of CSF-1R is phosphatidylinositol 3-kinase- and Cdc42-dependent consistent with an involvement of these molecules in macrophage migration, regulation, overview
metabolism
analysis of the mechanism by which phosphatidylinositol 4-phosphate 5-kinase Igammai2 and PI3K are integrated into a complex regulated by Src, resulting in the spatial generation of PIP2, which is the substrate PI3K required for PIP3 generation and subsequent Akt activation, the PIP2-generating enzyme controls Akt activation upstream of a PI3K enzyme
metabolism
the enzyme is involved in isoproterenol-induced EGFR transactivation
metabolism
analysis of the PI3K signaling cascade, overview
metabolism
-
inositol polyphosphate-4-phosphatase type II and rucaparib treatment inhibit the growth of osteosarcoma cells dependent on phosphoinositide 3-kinase/protein kinase B pathway, combined effects of INPP4B and rucaparib on cell cycle, apoptosis and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signal pathway. INPP4B plays an important role in the development of tumors, which can maintain the balance of internal inositol phosphate, suppress the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) signal pathway, and block cells malignant transformation
metabolism
PIK3CB/p110beta-dictated survival pathway in glioblastoma, overview
physiological function
-
activation of phosphatidylinositol 3-kinase is required for tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase-9
physiological function
-
isozyme PI3Kgamma is involved in inteleukin-8-induced increase of endothelial monolayer permeability and is able to limit neovascularization and choroidal edema, as well as macrophage infiltration, therefore contributes to reduce laser-induced retinal damage
physiological function
-
isozyme PI3Kgamma is involved in inteleukin-8-induced increase of endothelial monolayer permeability and is able to limit neovascularization and choroidal edema, as well as macrophage infiltration, therefore contributes to reduce laser-induced retinal damage
physiological function
-
p110 isoforms alpha, beta, and gamma PI3K are involved in T-cell acute lymphoblastic leukemia cell survival, but not p110delta PI3K
physiological function
-
phosphatidylinositol 3-kinase activity and asymmetrical accumulation of F-actin are necessary for establishment of cell polarity in the early development of monospores from the marine red alga. Establishment of the anterior-posterior axis in migrating monospores is PI3K-dependent
physiological function
-
phosphatidylinositol 3-kinase is a key mediator of oncogenic K-ras
physiological function
-
phosphatidylinositol 3-kinase is involved in sperm-induced tyrosine kinase signaling in Xenopus egg fertilization. Inhibition of sperm-induced activation of the tyrosine kinase Src and a transient increase in the intracellular concentration of Ca2+ at fertilization, overview. PIP3 acts as a positive regulator of the Src signaling pathway in Xenopus fertilization
physiological function
-
phosphatidylinositol 3-kinase mediates non-opsonic phagocytosis of Legionella pneumophila by macrophages
physiological function
-
PI 3-kinase activated in response to cAMP or IGF-I stimulus plays important roles in increasing the translation rate or mRNA levels of cyclin D1, respectively. Activation of PI 3-kinase in response to cAMP or IGF-I are essential for marked increases in G1 CDK activities and DNA synthesis. cAMP-dependent PI 3-kinase activation plays an important role in the increase in cyclin D1 translation. In contrast, IGF-I-dependent PI 3-kinase activation is required for the increase in cyclin D1 mRNA levels and degradation of p27Kip1
physiological function
-
PI 3-kinase is an important enzyme in the early insulin signaling cascade and plays a key role in insulin-mediated glucose transport
physiological function
-
PI3-kinase regulates Rac1 activity through the guanosine exchange factor Tiam1. Expression of mutant CA-PI3K causes a significant increase in membrane-associated Tiam1
physiological function
-
PI3K activation results in increased cell proliferation, motility, migration, and metastasis. Inhibition of PI3K signaling delays tumor progression and blocks metastasis of thyroid cancer
physiological function
-
PI3K, via p85alpha and p85beta subunit isoforms, plays dual regulatory roles in the induction of IFN responses by controlling both IFNalpha- and IFNgamma-dependent transcriptional regulation of IFN-sensitive genes and simultaneously regulating the subsequent initiation of mRNA translation for such genes
physiological function
-
selective regulation of CD8 effector T cell migration by the p110gamma catalytic subunit isoform of phosphatidylinositol 3-kinase
physiological function
-
the enzyme plays a pivotal role in the mechanism of CSF-1-induced Wiskott-Aldrich syndrome protein activation in vivo
physiological function
-
the p110gamma isoform of phosphatidylinositol 3-kinase regulates chemokine receptor-mediated migration of effector CD4 T lymphocytes into peripheral inflammatory sites. Although p110gamma does not regulate antigen-dependent CD4 T cell activation and proliferation, it plays a crucial role in regulating CD4 effector T cell migration, overview
physiological function
-
the p85alpha subunit of class IA phosphatidylinositol 3-kinase regulates the expression of multiple genes involved in osteoclast maturation and migration
physiological function
-
the signalling pathways regulated by class 1 PI3K signalling are central in many of the fundamental cellular processes associated with PI3K signalling including cell growth, proliferation, migration and survival, signaling pathway overview
physiological function
-
the signalling pathways regulated by class 1 PI3K signalling are central in many of the fundamental cellular processes associated with PI3K signalling including cell growth, proliferation, migration and survival, signaling pathway overview
physiological function
-
Tiam1-mediated Rac1 activation and E-cadherin-mediated cell-cell adhesion are dependent on PI3K activity, regulation, overview. The signaling hierarchy leads from PI3K to Tiam1 to Rac to the actin cytoskeleton resulting in adherens junction formation. PI3K is involved in E-cadherin-dependent regulation of epithelial cell differentiation and polarity
physiological function
-
Tiam1-mediated Rac1 activation and E-cadherin-mediated cell-cell adhesion are dependent on PI3K activity, regulation, overview. The signaling hierarchy leads from PI3K to Tiam1 to Rac to the actin cytoskeleton resulting in adherens junction formation. PI3K is involved in E-cadherin-dependent regulation of epithelial cell differentiation and polarity
physiological function
in tumor cell lines and primary patient samples representing multiple B-cell malignancies, constitutive phosphatidylinositol-3-kinase pathway activation is dependent on isoform PI3Kdelta. Inhibitor 3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one blocks constitutive phosphatidylinositol-3-kinase signaling, resulting in decreased phosphorylation of Akt and other downstream effectors, an increase in poly(ADP-ribose) polymerase and caspase cleavage and an induction of apoptosis
physiological function
-
isoform PI3Kdelta is responsible for phosphorylation of colony-stimulating factor CSF-1 receptor phosphorylation in response to CSF-1 added to intact cells or isolated nuclei and its triggering of the phosphorylation of Akt and p27 inside the nucleus. Translocation of exogenous CSF-1 to the nucleus-associated CSF-1 receptors correlates with a prominent role of isoform PI3Kdelta in activation of the Rab5 GTPase
physiological function
-
phosphatidylinositol 3-kinase is critical for the TLR2 downstream effects of glucocorticoids. Cells expressing a phosphatidylinositol 3-kinase p85 subunit deletion mutant and exposed to Pam3-Cys-Ser-Lys4 in the presence or absence of dexamethasone, show enhanced tumour necrosis factor TNFalpha expression while AP-1 and NF-kappaB transcriptional activity are repressed. Phosphatidylinositol 3-kinase physically interacts with the glucocorticoid receptor through two putative phosphatidylinositol 3-kinase recruitment consensus YxxM binding motifs in the glucocorticoid receptor. The phosphatidylinositol 3-kinase-glucocorticoid receptor interaction may contribute to the effects of glucocorticoids on the TLR2 pro-inflammatory signalling cascade
physiological function
phosphatidylinositol 3-kinase pathway inhibition is sufficient to reduce expression of Smad anchor for receptor activation protein, i.e. SARA. Phosphatidylinositol 3-kinase-dependent depletion of SARA is apparent within 6 h and does not occur at the mRNA or promoter level but is blocked by inhibition of proteasome-mediated degradation. It is a direct effect of phosphatidylinositol 3-kinase subunit alpha action, and coimmunoprecipitation of SARA and subunit alpha confirm that these proteins interact. Expression of GTPase-deficient Rab5 leads to endosomal enlargement and reduced SARA protein expression, similar to that seen with phosphatidylinositol 3-kinase inhibition
physiological function
-
suppressing phosphatidylinositol 3-kinase activity by inhibitors LY294002 and PI103 selectively reduces both the mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator PGC-1beta but not PGC-1alpha. Reducing PGC-1b expression also leads to reduced mRNA expression levels of uncoupling protein 1, 2 and superoxide dismutase 2. Correspondingly, mitochondrial membrane potential and reactive oxygen species levels are increased
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110alpha is crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of smooth muscle cells, Receptor tyrosine kinasesinduced phosphatidylinositol 3'-kinase signaling via the p110alpha isoform plays a central role for vascular remodeling
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110alpha is crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of smooth muscle cells, Receptor tyrosine kinasesinduced phosphatidylinositol 3'-kinase signaling via the p110alpha isoform plays a central role for vascular remodeling
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110alpha is crucial for receptor tyrosine kinases signaling, thus affecting proliferation, migration, and survival of smooth muscle cells, Receptor tyrosine kinasesinduced phosphatidylinositol 3'-kinase signaling via the p110alpha isoform plays a central role for vascular remodeling
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110beta is disensible for receptor tyrosine kinases signaling, not affecting proliferation, migration, and survival of smooth muscle cells
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110beta is disensible for receptor tyrosine kinases signaling, not affecting proliferation, migration, and survival of smooth muscle cells
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110delta is disensible for receptor tyrosine kinases signaling, p110delta exerts noncatalytic functions in smooth muscle cell proliferation, but had no effect on migration
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110delta is disensible for receptor tyrosine kinases signaling, p110delta exerts noncatalytic functions in smooth muscle cell proliferation, but had no effect on migration
physiological function
class Ia phosphatidylinositol 3-kinase isoform p110delta is disensible for receptor tyrosine kinases signaling, p110delta exerts noncatalytic functions in smooth muscle cell proliferation, but had no effect on migration
physiological function
enzyme PI3K is rapidly recruited to activated growth factor receptors (SH2 domain of the adaptor subunit mediating the interaction to the phosphorylated YXXM motif of the receptor) or integrin-mediated adhesion complex (via interaction with focal adhesion kinase in the adhesion complex), promoting its activation and 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate synthesis. phosphatidylinositol 4-phosphate 5-kinase Igamma, EC 2.7.1.68, is the major PIPKI enzyme contributing to PI3K/Akt signaling in response to activation of growth factor and adhesion receptors in suspension condition, overview
physiological function
non-canonical regulation of phosphatidylinositol 3-kinase gamma isoform activity in retinal rod photoreceptor cells. The interaction between the gamm isozyme and alpha subunit of cyclic nucleotide-gated channel, CNGA1, through its RA domain does not appear to play a role in regulation of CNG channel activity, but phosphatidylinositol 3-kinase gamma uses CNGA1 as an anchoring module to achieve close proximity to its substrate to generate D3-phosphoinositides. CNGA1-associated PI3Kgamma activity is independent of dark and light conditions, as well as insulin receptor impairment in rods. The RA domain of isozyme PI3Kgamma interacts strongly with CTR-CNGA1, compared with the RA domain of isozyme PI3Kalpha in retinal photoreceptor cells
physiological function
-
phosphatidylinositol 3-kinase gamma is central in signaling diverse cellular functions. Relevance of isozyme PI3Kgamma for the outcome and the neuroinflammatory process triggered by Plasmodium berghei ANKA infection
physiological function
phosphatidylinositol 4,5-bisphosphate is essential for recognition of the plasma membrane inner leaf by protein complexes. Elimination of phosphatidylinositol 4,5-bisphosphate by its conversion into 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate, a lipid naturally missing in this yeast. The loss of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate leads to loss of actin function and endocytosis defects, causing a blockage in polarized secretion. Also, the cell wall integrity mitogen-activated protein kinase pathway is activated, triggering a typical transcriptional response. In the absence of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate at the plasma membrane, the Pkc1 protein kinase upstream the cell wall integrity mitogen-activated protein kinase pathway module localizes to post-Golgi endosomes marked by SNARE Snc1 and Rab GTPases Ypt31 and Ypt32. Phosphatidylinositol 4,5-bisphosphate depletion activates the CWI pathway and generates a transcriptional profile reminiscent of that induced by cellwall aggressions. PI3K effects in yeast signaling and trafficking are reversible by a competitive inhibitor in a dose-dependent manner
physiological function
phosphoinositide 3-kinase (PI3K) is a dual specificity kinase that is known to be involved in cell survival and malignant transformation, and it is able to phosphorylate both lipid and protein substrates. PI3K protein kinase activity can directly phosphorylate growth factor receptors on human hematopoietic (blood) cells to promote a survival-only response. The protein kinase activity but not the lipid kinase activity of PI3K promotes cytokine-mediated cell survival. The PI3K lipid kinase activity is not essential for regulating cell survival
physiological function
the generation of phosphatidylinositol (3,4,5)-tris-phosphate (PIP3) by the lipid kinase function stabilizes beta2AREGFR complexes while the protein kinase activity of PI3K regulates Src activation by direct phosphorylation. The lipid kinase activity of PI3K is responsible for beta2AREGFR complex formation. Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation. EGFR transactivation is a mechanism by which the EGF receptor is stimulated, internalized, and downstream signaling initiated following agonist stimulation by a GPCR, such as the beta-adrenergic receptor. The protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following beta-adrenergic receptor stimulation. This additional function for PI3K, whereby Src is a substrate for the protein kinase activity of enzyme PI3K, is of importance since Src plays a key role in pathological and physiological signaling
physiological function
the PI3Kalpha signaling pathway plays an important role in cell growth, proliferation and survival. This pathway is activated in numerous cancers, where the PI3KCA gene, which encodes for the p110alpha PI3Kalpha subunit, is mutated. Physiological activation of PI3Kalpha is triggered by binding of phosphorylated tyrosine kinase receptors RTK or their accessory proteins, such as the insulin receptor substrate 1, IRS-1, that bridge the interaction between RTK and PI3Kalpha
physiological function
phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in the pathogenesis of cancer including glioblastoma, the most common and aggressive form of brain cancer. Analysis of the role of class IA PI3K catalytic subunits in glioblastoma, overview. siRNAs or shRNAs of PIK3CB, but not shRNAs of PIK3CA, inhibits the growth of U-87MG cells. Subunit PIK3CD/p110beta plays a dispensable role in the disease progression of glioblastoma. Receptor tyrosine kinases (RTKs) or G protein-coupled receptors (GPCRs) selectively activates PIK3CB/p110beta (but not PIK3CA/p110alpha or PIK3CD/p110delta), leading to production of phosphatidylinositol-3,4,5-triphosphate (PIP3) and subsequent phosphorylation of AKT. Divergent roles of class I PI3K genes in normal and malignant tissues, overview
physiological function
phosphatidylinositol-4,5-bisphosphate 3-kinases (PI3Ks) are regulatory enzymes involved in the generation of lipid species that modulate cellular signaling pathways through downstream effectors to influence a variety of cellular functions. Stimulation of PI3K can enhance lysosomal trafficking events to the plasma membrane. Insulin-induced activation of PI3K alters glucose transporter GLUT4 recycling, positive regulatory role for PI3K pathway in the GLUT4 receptor recycling process. PI3K demonstrates both positive and negative regulation of insulin release. The p110gamma subunit of type I PI3K is required to maintain a ready pool of insulin loaded vesicles for the recruitment of insulin granules in the islet beta-cells for release upon exocytic stimulation. PI3K C2alpha, a class II PI3K isoform, exerts signaling effects on insulin secretion from pancreatic beta-cells by promoting insulin loaded granules in insulinoma cells. PI3K is also known to contribute to glucose homeostasis by regulating beta-cell gene expression
physiological function
-
phosphatidylinositol 3-kinase activity and asymmetrical accumulation of F-actin are necessary for establishment of cell polarity in the early development of monospores from the marine red alga. Establishment of the anterior-posterior axis in migrating monospores is PI3K-dependent
-
physiological function
-
selective regulation of CD8 effector T cell migration by the p110gamma catalytic subunit isoform of phosphatidylinositol 3-kinase
-
physiological function
-
phosphatidylinositol 3-kinase gamma is central in signaling diverse cellular functions. Relevance of isozyme PI3Kgamma for the outcome and the neuroinflammatory process triggered by Plasmodium berghei ANKA infection
-
additional information
-
SHIP downregulates PI3-K-initiated signals by dephosphorylating PI-3,4,5-triphosphate
additional information
N-terminal tags on the catalytic (p110) subunit of phosphoinositol 3-kinase increase cell signalling and oncogenic transformation, the increase in cell signalling and oncogenic-like transformation in response to p110 NTT is not mediated via an increase in the lipid kinase activity of the enzyme, but may be mediated by increased p110 autophosphorylation and/or other intracellular protein/protein interactions. Tagged recombinant protein is suitable for use in in vitro lipid kinase screens to identify phosphoinositol 3-kinase inhibitors, while in vivo (including intracellular) experiments and investigations into the protein kinase activity should be conducted with untagged constructs
additional information
N-terminal tags on the catalytic (p110) subunit of phosphoinositol 3-kinase increase cell signalling and oncogenic transformation, the increase in cell signalling and oncogenic-like transformation in response to p110 NTT is not mediated via an increase in the lipid kinase activity of the enzyme, but may be mediated by increased p110 autophosphorylation and/or other intracellular protein/protein interactions. Tagged recombinant protein is suitable for use in in vitro lipid kinase screens to identify phosphoinositol 3-kinase inhibitors, while in vivo (including intracellular) experiments and investigations into the protein kinase activity should be conducted with untagged constructs
additional information
the class IA PI3K gene family consists of three highly homologous catalytic subunits PIK3CA, PIK3CB, and PIK3CD (PI3K catalytic subunit alpha, beta, and delta) that encode p110alpha, p110beta, and p110delta, respectively. These subunits form a complex with any of five regulatory subunits p85alpha, p55alpha (a splicing variant of p85alpha), p50alpha (a splicing variant of p85alpha), p85beta, and p55gamma, encoded by PIK3R1, PIK3R2, and PIK3R3 (PI3K regulatory subunit 1, 2, and 3), respectively. Class IB PI3K is composed of one catalytic subunit p110gamma encoded by PIK3CG (PI3K catalytic subunit gamma)and two regulatory subunits: p101 encoded by PIK3R5 (PI3K regulatory subunit 5) and p87 (also known as p84 or p87PIKAP) encoded by PIK3R6 (PI3K regulatory subunit 6). The amino acid K342 in wild-type p110beta exhibits structural changes (i.e. disrupted interactions between p110beta and its regulatory partner p85), which endows p110beta with an unusually high transformation potential similar to the oncogenic p110alpha mutant p110alpha-N345K
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x * 119471, p110delta subunit, can bind the p85 adaptor subunit, calculation from nucleotide sequence
?
x * 119505, calculated, x * 110000, SDS-PAGE
?
x * 120000, calculated, x * 110000, SDS-PAGE
dimer
-
class I PI3Ks exist as heterodimers consisting of one of four p110 catalytic subunit isoforms and one of two families of regulatory subunit forms. PI3K class III has only one member known as Vps34
dimer
-
PI3 kinases are heterodimers comprised of a regulatory subunit p85 and a catalytic subunit p110. Class IA subunit p110, i.e. PIK3CA, exists in three isoforms, p110alpha, p110beta, and p110gamma. All have similar structure with domains for binding to the adaptor protein subunit PIK3R1, p85, and to RAS
dimer
-
regulatory p85alpha and p85beta subunits of class IA PI3-K share near identity in the functional domains in the C-terminus, including the amino-SH2 and the carboxy-SH2 domains, which are critical for mediating association with other SH2-containing proteins as well as binding to the p110 catalytic subunit
heterodimer
-
catalytic subunit p110 and regulatory subunit p85
heterodimer
-
catalytic subunit p110 and regulatory subunit p85
heterodimer
-
catalytic subunit p110alpha and regulatory subunit p85. p85 binding to p110alpha is required for activity
heterodimer
-
PI3K is formed by a catalytic subunit p110, occuring in four isoforms p110alpha, p110beta, p110gamma, and p110delta, and a regulatory subunit p85
heterodimer
-
the catalytic subunits of the class IA PI3Ks form heterodimers with one of five Src-homology 2, SH2, domain-containing regulatory subunits p85alpha, p85beta, p55alpha, p55gamma and p50alpha, which bind with high affinity to phosphorylated tyrosines of receptor tyrosine kinases
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110alpha) and a smaller regulatory subunit (p85)
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110beta) and a smaller regulatory subunit (p85)
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110delta) and a smaller regulatory subunit (p85)
heterodimer
1* 85000, alpha-subunit, + 1 * 110000, beta-subunit
heterodimer
-
catalytic subunit p110 and regulatory subunit p85
heterodimer
-
the catalytic subunits of the class IA PI3Ks form heterodimers with one of five Src-homology 2, SH2, domain-containing regulatory subunits p85alpha, p85beta, p55alpha, p55gamma and p50alpha, which bind with high affinity to phosphorylated tyrosines of receptor tyrosine kinases
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110alpha) and a smaller regulatory subunit (p85)
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110delta) and a smaller regulatory subunit (p85)
heterodimer
-
a p110alpha/beta-subunit binds to a p85 regulatory subunit, and this heterodimer is recruited to the membrane through the association with phosphotyrosyl proteins, leading to production of phosphatidylinositol 3,4,5-triphosphate, PIP3, followed by activation of downstream signal pathway(s)
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110alpha) and a smaller regulatory subunit (p85)
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110beta) and a smaller regulatory subunit (p85)
heterodimer
1 * 110000, subunit p110, + 1 * 85000, subunit p85, class IA PI3K isoforms are heterodimers consisting of a catalytic subunit (p110delta) and a smaller regulatory subunit (p85)
additional information
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class I phosphoinositide 3-kinases are heterodimers made up of an catalytic subunit, called p110, of about 110000 Da and an adaptor/regulatory subunit. Class I phosphoinositide 3-kinases are further subdivided into class Ia and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively
additional information
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a single type of catalytic/adaptor heterodimer: AGE-1/AAP-1
additional information
-
class I phosphoinositide 3-kinases are heterodimers made up of an catalytic subunit, called p110, of about 110000 Da and an adaptor/regulatory subunit. Class I phosphoinositide 3-kinases are further subdivided into class Ia and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively
additional information
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three catalytic subunits: PIK1, PIK2 or PIK3
additional information
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class I phosphoinositide 3-kinases are heterodimers made up of an catalytic subunit, called p110, of about 110000 Da and an adaptor/regulatory subunit. Class I phosphoinositide 3-kinases are further subdivided into class Ia and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively
additional information
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a single type of catalytic/adaptor heterodimer: Dp110/p60
additional information
a 187 amino acid domain of regulatory subunit p85 mediates interaction with catalytic subunit p110 in vitro and in intact cells
additional information
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a 187 amino acid domain of regulatory subunit p85 mediates interaction with catalytic subunit p110 in vitro and in intact cells
additional information
-
enzyme forms a complex with a phosphatidylinositol-(3,4,5)-triphosphate 5-phosphatase distinct from platelet 43 kDa and 75kDa 5-phosphatases
additional information
forms a complex with regulatory subunit p85
additional information
-
forms a complex with regulatory subunit p85
additional information
G-protein beta,gamma recruits the enzyme from the cytosol to the mebrane by interaction with ist p101 subunit
additional information
no interaction with regulatory subunit p85
additional information
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specific interaction between GTPase Rab5 and enzyme catalytic subunit p110beta leading to efficient coupling of enzyme product to its downstream target, protein kinase B
additional information
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p85alpha subunit of class I PI3K
additional information
the heterodimers consisting of an 85 kDa regulatory/adapter subunit (p85) coupled to a 110 kDa catalytic subunit (p110) with both subunits possessing several isoforms
additional information
the heterodimers consisting of an 85 kDa regulatory/adapter subunit (p85) coupled to a 110 kDa catalytic subunit (p110) with both subunits possessing several isoforms
additional information
the class IA PI3K gene family consists of three highly homologous catalytic subunits PIK3CA, PIK3CB, and PIK3CD (PI3K catalytic subunit alpha, beta, and delta) that encode p110alpha, p110beta, and p110delta, respectively. These subunits form a complex with any of five regulatory subunits p85alpha, p55alpha (a splicing variant of p85alpha), p50alpha (a splicing variant of p85alpha), p85beta, and p55gamma, encoded by PIK3R1, PIK3R2, and PIK3R3 (PI3K regulatory subunit 1, 2, and 3), respectively. Class IB PI3K is composed of one catalytic subunit p110gamma encoded by PIK3CG (PI3K catalytic subunit gamma) and two regulatory subunits: p101 encoded by PIK3R5 (PI3K regulatory subunit 5) and p87 (also known as p84 or p87PIKAP) encoded by PIK3R6 (PI3K regulatory subunit 6). PI3K catalytic subunits (PIK3CA/p110alpha, PIK3CB/p110beta, PIK3CD/p110delta, and PIK3CG/p110gamma) are not functionally redundant
additional information
-
-
additional information
-
class I phosphoinositide 3-kinases are heterodimers made up of an catalytic subunit, called p110, of about 110000 Da and an adaptor/regulatory subunit. Class I phosphoinositide 3-kinases are further subdivided into class Ia and IB enzymes, which signal downstream of tyrosine kinase and heterotrimeric G protein-coupled receptors, respectively
additional information
-
three class IA p110 isoforms, p110alpha, beta and delta, which are encoded by three separate genes, at least seven adaptor proteins, which are generated by expression and alternative splicing of three different genes, namely p85alpha, p85beta and p55gamma. All these splice variants make functional complexes with p110 subunits
additional information
-
enzyme is comprised of p110 catalytic subunit and a regulatory subunit often derived of p85. In wild-type cells, p85 subunit is more abundant than p110
additional information
interactive domains in subunits p85 and p110 responsible for binding to each other are less than 103 and 124 amino acids, respectively. Association of subunits is critical for enzyme activity
additional information
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interactive domains in subunits p85 and p110 responsible for binding to each other are less than 103 and 124 amino acids, respectively. Association of subunits is critical for enzyme activity
additional information
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p85 regulatory subunit forms cytosolic complexes with insulin receptor substrate
additional information
-
regulatory p85 and catalytic p110 subunits are present in equimolar amounts in mammalian cell lines and tissues. No evidence for free p85 or p110 subunits could be obtained. Cell lines contain 10,000-15,000 p85/p110 complexes per cell, with p110beta and p110delta being the most prevalent catalytic subunits in nonleukocytes and leukocytes, respectively
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M582V
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site-directed mutagenesis, the full-length p85alpha isoform inter-SH2 domain mutation enables the mutant PI3K to bind influenza A virus NS1 protein leading to activation of the mutant PI3K enzyme activity, molecular modeling, overview
V573M
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site-directed mutagenesis, the p85beta isoform inter-SH2 domain mutation abrogates mutant PI3K binding to influenza A virus NS1 protein, molecular modeling, overview
A1066V
-
a common naturally occuring mutation involved in cancer development
D1017H
-
a common naturally occuring somatic mutation involved in cancer development
D915A
complete loss of enzymic activity
D933A/F934A
complete loss of enzymic activity
E542K
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a common naturally occuring mutation in the helical domain, the mutation is involved in cancer development, the mutant requires RAS binding but bot p85 binding
E545K/H1047R
-
gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation
E970A
90% of wild-type activity
K227E
-
the mutaion reduces enzyme activity
K802R
mutation in subunit p110alpha, inactive mutant
M1043I
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a common naturally occuring somatic mutation involved in cancer development
M326I
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a common naturally occuring polymorphism of the regulatory subunit p85alpha in women involved in the polycystic ovary syndrome, PCOS, genotyping in polycystic ovary syndrome patients from Korean female population
P124L
-
a common naturally occuring somatic mutation involved in cancer development. P124L lies in a region of four helices in the protein between the adapter-binding and RAS-binding domains
P124T
-
a naturally occuring missense mutation in codon 124 from a colorectal cancer cell
Q643R
-
a common naturally occuring somatic mutation involved in cancer development
R274A
-
the GTPase-activating protein activity toward Rab5 and Rab4 of PI3K p85alpha subunit is abolished in the mutant. Expression of p85alpha-R274A results in increased platelet-derived growth factor receptor, PDGFR, activation and downstream signaling, via Akt and MAPK pathways, and in decreased PDGFR degradation. Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation, co-expression of a dominant negative Rab5-S34N mutant attenuates these transformed properties
R38C/R88C
the mutation significantly change the distance distribution for helical domain residues K379, I381 and K382
R922A
80% of wild-type activity
M582V
-
site-directed mutagenesis, the full-length p85alpha isoform inter-SH2 domain mutation enables the mutant PI3K to bind influenza A virus NS1 protein leading to activation of the mutant PI3K enzyme activity, molecular modeling, overview
V573M
-
site-directed mutagenesis, the p85beta isoform inter-SH2 domain mutation abrogates mutant PI3K binding to influenza A virus NS1 protein, molecular modeling, overview
E542K/E545K
-
gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation
E542K/E545K
the mutation disrupts the interaction between residues E545 (helical domain) and K379 (nSH2 domain)
E545K
-
a common naturally occuring mutation in the helical domain, the mutation is involved in cancer development, the mutant requires RAS binding but bot p85 binding
E545K
site-directed mutagenesis of p110alpha, an oncogenic mutant enzyme form
H1047R
-
a common naturally occuring mutation of the kinase domain, that is involved in cancer development
H1047R
-
gain-of-function mutation of subunit p110alpha, the H1047R mutation can substitute for RAS binding, but binding to p85 is essential for H1047R-induced cell transformation
H1047R
site-directed mutagenesis of p110alpha, an oncogenic mutant enzyme form
N345K
the mutation significantly change the distance distribution for helical domain residues K379, I381 and K382
N345K
a naturally occuring oncogenic p110alpha mutant
D910A
-
site-directed mutagenesis of isoform p110delta, catalytically inactive. Interleukin is unable to induce hyper-responsiveness in tissues expressing the mutant
D910A
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mice with an inactivating knock-in mutation in the p110delta isoform of PI3K, p110deltaD910A, generated on Leishmanina major resistant and susceptible genetic backgrounds. The mutant mice show severely impaired T cell responses, but the mutant mice also show more robust resistance to Leishmanina major infection manifested as significantly reduced lesion size and accelerated parasite clearance. Cells from p110D910A mice were significantly impaired in their ability to make cytokines, particularly IFN-gamma, interleukin-10, and TNF, phenotypes, overview
additional information
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construction of chimeras of 85alpha and p85beta iSH2 domain by overlapping PCR using mouse p85beta and bovine p85alpha as templates
additional information
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a mutant with a deletion in the binding site of the p110 catalytic subunit is dominant negative
additional information
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a mutant with a deletion in the binding site of the p110 catalytic subunit is dominant negative
additional information
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construction of a constitutively active PI3-kinase, CA-PI3K, mutant, whose expression stimulates translocation of Tiam1 to the membrane, increases Rac1 activity, and increases wound healing of airway epithelial cells, phenotype, overview. Expression of a dominant negative form of PI3-kinase,using an adenoviral vector, causes inhibition of airway epithelial cell wound closure, overview
additional information
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construction of a dominant negative PI3K mutant by PCR cloning. Legionella pneumophila entry into macrophages expressing the mutant is reduced
additional information
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deficiency of PI3-K regulatory subunit p85alpha in vivo results in a significantly greater number of trabeculae and significantly lower spacing between trabeculae as well as increased bone mass in both males and females compared to their sex-matched wild-type controls. p85-/- osteoclast progenitors show impaired growth and differentiation, which is associated with reduced activation of Akt and mitogen-activated protein kinase Erk1/Erk2 in vitro, and a significant reduction in the ability of p85-/- osteoclasts to adhere to as well as to migrate via integrin alphanybeta3. Restoring the expression of the full-length form of p85alpha but not the version with a deletion of the Src homology-3 domain restores the maturation of p85-/- osteoclasts to wild-type levels, overview. Phenotypes, overview
additional information
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genetic abolition of PI3Kdelta signalling by insertion of a kinase-dead p110delta catalytic subunit results in impaired B cell and T cell antigen receptor signalling
additional information
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helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms, overview. About 30% of prostate, breast, cervix, and endometrium tumors show catalytic subunit p110alpha mutations, the most prominent single amino acid substitutions in the helical or kinase domain result in a gain of enzymatic function, activate AKT signaling, and induce oncogenic transformation, analysis of hot-spot mutations in gene PIK3CA. The gain of function induced by helical domain mutations is independent of binding to p85 but requires interaction with RAS-GTP. In contrast, the kinase domain mutation is active in the absence of RAS-GTP binding but is highly dependent on the interaction with p85. Truncation reduce the activities of all enzymes, truncated wild-type and mutant, overview. Phenotypes, overview
additional information
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mutations in PIK3CA are also found commonly in the benign skin lesions seborrheic keratosis and epidermal nevi
additional information
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sequencing of cancer cell p85alpha subunits reveal four mutational alterations, three colonic and one ovarian: one with an early stop codon after Asp605 and three containing small in-frame deletions, DELTALeu570-Gln572, DELTALeu570-Asp578, and DELTAMet582-Asp605. These deletions are located near the negative regulatory phosphorylation site Ser608 within p85alpha. All mutations lead to increased enzyme activity
additional information
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suppression of the PI3K catalytic subunit p110alpha inhibits the growth of ovarian cancer cells in vitro and in vivo
additional information
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the most common sites for hotspot mutations of PI3Kalpha are around amino acid 1047 in the kinase domain, and amino acid 545 in the helical domain, the mutations are involved in breast and colon tumorigenesis
additional information
determination of p110alpha subunit oncogenic mutations disrupt the interactions at the p110alpha-p85alpha interface, overview. Even distant mutations (R38C/R88Q and N345K) effectively weaken the interaction between the nSH2 and helical domain, thus increasing the population of molecules that are not inhibited by the the nSH2 domain. The oncogenic mutations increase the conformational heterogeneity of the p85alpha subunit and lead to PI3Kalpha activation by releasing the p85? nSH2 inhibitory effect
additional information
N-terminal tags on the catalytic (p110) subunit of phosphoinositol 3-kinase increase cell signalling and oncogenic transformation
additional information
N-terminal tags on the catalytic (p110) subunit of phosphoinositol 3-kinase increase cell signalling and oncogenic transformation
additional information
overexpression of the GFP-tagged PH domain of Akt1 blocks the binding of endogenous PH-domain proteins (such as Akt) to phosphatidyl inositol phosphates in the plasma membrane thereby abrogating PI3K lipid signaling but permitting PI3K protein kinase signaling
additional information
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overexpression of the GFP-tagged PH domain of Akt1 blocks the binding of endogenous PH-domain proteins (such as Akt) to phosphatidyl inositol phosphates in the plasma membrane thereby abrogating PI3K lipid signaling but permitting PI3K protein kinase signaling
additional information
p110 subunit knockdown via specific siRNA application
additional information
p110 subunit knockdown via specific siRNA application
additional information
p110 subunit knockdown via specific siRNA application
additional information
-
p110 subunit knockdown via specific siRNA application
additional information
knockdown of PIK3CA/p110alpha in a panel of glioblastoma cell lines
additional information
somatic gain of function PIK3CA-mutation due to a pathogenic heterozygous missense mutation in PIK3CA, phenotype, overview
additional information
expression of regulatory protein p85 102 amino acid binding domain plus catalytic subunit p110 leads to fully active enzyme complex
additional information
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expression of regulatory protein p85 102 amino acid binding domain plus catalytic subunit p110 leads to fully active enzyme complex
additional information
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heterozygous disruption of p85alpha regulatory subunit, increase in enzyme activity and decrease in apoptosis by insulin-like growth factor 1 through upregulated phosphatidylinositol (3,4,5)-triphosphate production. Complete depletion of regulatory subunit p85alpha results in significantly increased apoptosis due to reduced enzyme-dependent signaling
additional information
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genetic deletion or selective inhibition of isoform PI3Kdelta diminishes joint erosion to a level comparable to its PI3Kgamma counterpart. The induction and progression of joint destruction is profoundly reduced in the absence of both PI3K isoforms and correlates with a limited ability of neutrophils to migrate into tissue in response to leukotriene B4. fMLP-induced neutrophil extravasation is primarily reliant on PI3Kgamma
additional information
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construction of chimeras of 85alpha and p85beta iSH2 domain by overlapping PCR using mouse p85beta and bovine p85alpha as templates
additional information
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generation of different transgenic lines expressing myristoylated p110A protein under the control of the epithelial-specific mouse mammary tumor virus promoter, i.e. myrp110A transgenic mice. The membrane localization of p110alpha predisposes mammary glands to neoplastic transformation, young female mutant mice show delayed mammary gland involution and morphologic changes of the mammary ducts, which is more pronounced in old animals, especially in mutiparous females, in which increased ductal branching, alveolar hyperplasia, and intraductal neoplasia are observed, phenotype, overview
additional information
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generation of p110gamma knockout mice. p110gamma-deficient effector CD8 T cells exhibit impaired migration in vitro and exhibit reduced migration into the inflamed peritoneum following vaccinia virus challenge in vivo. Furthermore, p110gamma-/- mice exhibit reduced influx in response to virus-induced peritonitis and exhibit increased susceptibility to vaccinia virus infection when compared with wild-type mice, phenotype, overview
additional information
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mRNA translation of IFN-responsive genes is defective in cells with targeted disruption of both the p85alpha and p85beta subunits of PI3K
additional information
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mutations in catalytic subunit PI3Kdelta, PI3KdD910/A910 mice display impaired B cell development and differentiation including a reduction in B cell progenitor cells and an increase in the ratio of pre-(CD43-IgM+) to pro-(CD43+ IgM-) B cells. T cell differentiation into Th1, Th2 and Treg lineages are also impaired in PI3KdD910/A910 mice by a mechanism involving reduced T cell receptor activation of Akt and FOXO
additional information
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p110-/- CD4 lymphocytes are phenotypically identical to their wild-type counterparts and do not exhibit any defects in TCR-mediated calcium mobilization or Erk activation. p110gamma-deficient CD4 OT.II T cells become activated and proliferate comparably with WT cells in response to antigen in vivo. But antigen-experienced p110gamma-deficient CD4 OT.II lymphocytes exhibit dramatic defects in their ability to traffic to peripheral inflammatory sites in vivo and exhibit impaired F-actin polarization and migration in response to stimulation ex vivo with the CCR4 ligand CCL22
additional information
generation of a mouse model of smooth muscle cellspecific p110alpha deficiency. Targeted deletion of p110alpha in sm-p110alpha-/- mice blunts growth factorinduced cellular responses and abolishes neointima formation after balloon injury of the carotid artery in mice. p110 Subunit knockdown via specific siRNA application
additional information
generation of a mouse model of smooth muscle cellspecific p110alpha deficiency. Targeted deletion of p110alpha in sm-p110alpha-/- mice blunts growth factorinduced cellular responses and abolishes neointima formation after balloon injury of the carotid artery in mice. p110 Subunit knockdown via specific siRNA application
additional information
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generation of a mouse model of smooth muscle cellspecific p110alpha deficiency. Targeted deletion of p110alpha in sm-p110alpha-/- mice blunts growth factorinduced cellular responses and abolishes neointima formation after balloon injury of the carotid artery in mice. p110 Subunit knockdown via specific siRNA application
additional information
generation of a mouse model of smooth muscle cellspecific p110delta deficiency. Targeted deletion of p110delta doe not affect vascular remodeling in vivo. p110 Subunit knockdown via specific siRNA application
additional information
generation of a mouse model of smooth muscle cellspecific p110delta deficiency. Targeted deletion of p110delta doe not affect vascular remodeling in vivo. p110 Subunit knockdown via specific siRNA application
additional information
-
generation of a mouse model of smooth muscle cellspecific p110delta deficiency. Targeted deletion of p110delta doe not affect vascular remodeling in vivo. p110 Subunit knockdown via specific siRNA application
additional information
-
generation of PI3Kgamma-deficient mice
additional information
-
generation of p110gamma knockout mice. p110gamma-deficient effector CD8 T cells exhibit impaired migration in vitro and exhibit reduced migration into the inflamed peritoneum following vaccinia virus challenge in vivo. Furthermore, p110gamma-/- mice exhibit reduced influx in response to virus-induced peritonitis and exhibit increased susceptibility to vaccinia virus infection when compared with wild-type mice, phenotype, overview
-
additional information
-
generation of PI3Kgamma-deficient mice
-
additional information
-
p110 subunit knockdown via specific siRNA application
additional information
p110 subunit knockdown via specific siRNA application
additional information
p110 subunit knockdown via specific siRNA application
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Selective regulation of CD8 effector T cell migration by the p110 gamma isoform of phosphatidylinositol 3-kinase
J. Immunol.
180
2081-2088
2008
Mus musculus, Mus musculus C57BL/6
brenda
Kaur, S.; Sassano, A.; Joseph, A.M.; Majchrzak-Kita, B.; Eklund, E.A.; Verma, A.; Brachmann, S.M.; Fish, E.N.; Platanias, L.C.
Dual regulatory roles of phosphatidylinositol 3-kinase in IFN signaling
J. Immunol.
181
7316-7323
2008
Mus musculus
brenda
Liu, D.; Zhang, T.; Marshall, A.J.; Okkenhaug, K.; Vanhaesebroeck, B.; Uzonna, J.E.
The p110delta isoform of phosphatidylinositol 3-kinase controls susceptibility to Leishmania major by regulating expansion and tissue homing of regulatory T cells
J. Immunol.
183
1921-1933
2009
Mus musculus
brenda
Thomas, M.S.; Mitchell, J.S.; DeNucci, C.C.; Martin, A.L.; Shimizu, Y.
The p110gamma isoform of phosphatidylinositol 3-kinase regulates migration of effector CD4 T lymphocytes into peripheral inflammatory sites
J. Leukoc. Biol.
84
814-823
2008
Mus musculus
brenda
Ihle, N.T.; Powis, G.
Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy
Mol. Cancer Ther.
8
1-9
2009
Homo sapiens
brenda
Munugalavadla, V.; Vemula, S.; Sims, E.C.; Krishnan, S.; Chen, S.; Yan, J.; Li, H.; Niziolek, P.J.; Takemoto, C.; Robling, A.G.; Yang, F.C.; Kapur, R.
The p85alpha subunit of class IA phosphatidylinositol 3-kinase regulates the expression of multiple genes involved in osteoclast maturation and migration
Mol. Cell. Biol.
28
7182-7198
2008
Homo sapiens
brenda
Gavard, J.; Hou, X.; Qu, Y.; Masedunskas, A.; Martin, D.; Weigert, R.; Li, X.; Gutkind, J.S.
A role for a CXCR2/phosphatidylinositol 3-kinase gamma signaling axis in acute and chronic vascular permeability
Mol. Cell. Biol.
29
2469-2480
2009
Homo sapiens, Mus musculus
brenda
Chen, B.C.; Kang, J.C.; Lu, Y.T.; Hsu, M.J.; Liao, C.C.; Chiu, W.T.; Yeh, F.L.; Lin, C.H.
Rac1 regulates peptidoglycan-induced nuclear factor-kappaB activation and cyclooxygenase-2 expression in RAW 264.7 macrophages by activating the phosphatidylinositol 3-kinase/Akt pathway
Mol. Immunol.
46
1179-1188
2009
Mus musculus
brenda
Zhang, X.; Deng, H.X.; Zhao, X.; Su, D.; Chen, X.C.; Chen, L.J.; Wei, Y.Q.; Zhong, Q.; Li, Z.Y.; He, X.; Yi, T.
RNA interference-mediated silencing of the phosphatidylinositol 3-kinase catalytic subunit attenuates growth of human ovarian cancer cells in vitroand in vivo
Oncology
77
22-32
2009
Homo sapiens
brenda
Yang, Y.; Iwanaga, K.; Raso, M.G.; Wislez, M.; Hanna, A.E.; Wieder, E.D.; Molldrem, J.J.; Wistuba, I.I.; Powis, G.; Demayo, F.J.; Kim, C.F.; Kurie, J.M.
Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer
PLoS ONE
3
e2220
2008
Mus musculus
brenda
Tachado, S.D.; Samrakandi, M.M.; Cirillo, J.D.
Non-opsonic phagocytosis of Legionella pneumophila by macrophages is mediated by phosphatidylinositol 3-kinase
PLoS ONE
3
e3324
2008
Homo sapiens
brenda
Zhao, L.; Vogt, P.K.
Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms
Proc. Natl. Acad. Sci. USA
105
2652-2657
2008
Homo sapiens
brenda
Akashi, T.; Yamori, T.
Proteomic analysis of phosphoproteins sensitive to a phosphatidylinositol 3-kinase inhibitor, ZSTK474, by using SELDI-TOF MS
Proteome Sci.
7
14
2009
Homo sapiens
brenda
Furuya, F.; Lu, C.; Guigon, C.J.; Cheng, S.Y.
Nongenomic activation of phosphatidylinositol 3-kinase signaling by thyroid hormone receptors
Steroids
74
628-634
2009
Mus musculus
brenda
Marwick, J.A.; Chung, K.F.; Adcock, I.M.
Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease
Ther. Adv. Respir. Dis.
2009
1-16
2010
Homo sapiens, Mus musculus
brenda
Lin, H.; Erhard, K.; Hardwicke, M.A.; Luengo, J.I.; Mack, J.F.; McSurdy-Freed, J.; Plant, R.; Raha, K.; Rominger, C.M.; Sanchez, R.M.; Schaber, M.D.; Schulz, M.J.; Spengler, M.D.; Tedesco, R.; Xie, R.; Zeng, J.J.; Rivero, R.A.
Synthesis and structure-activity relationships of imidazo[1,2-a]pyrimidin-5(1H)-ones as a novel series of beta isoform selective phosphatidylinositol 3-kinase inhibitors
Bioorg. Med. Chem. Lett.
22
2230-2234
2012
Homo sapiens (P42338)
brenda
Sanchez, R.M.; Erhard, K.; Hardwicke, M.A.; Lin, H.; McSurdy-Freed, J.; Plant, R.; Raha, K.; Rominger, C.M.; Schaber, M.D.; Spengler, M.D.; Moore, M.L.; Yu, H.; Luengo, J.I.; Tedesco, R.; Rivero, R.A.
Synthesis and structure-activity relationships of 1,2,4-triazolo[1,5-a]pyrimidin-7(3H)-ones as novel series of potent beta isoform selective phosphatidylinositol 3-kinase inhibitors
Bioorg. Med. Chem. Lett.
22
3198-3202
2012
Homo sapiens (P42338)
brenda
Large, J.M.; Torr, J.E.; Raynaud, F.I.; Clarke, P.A.; Hayes, A.; Stefano, F.d.; Urban, F.; Shuttleworth, S.J.; Saghir, N.; Sheldrake, P.; Workman, P.; McDonald, E.
Preparation and evaluation of trisubstituted pyrimidines as phosphatidylinositol 3-kinase inhibitors. 3-Hydroxyphenol analogues and bioisosteric replacements
Bioorg. Med. Chem.
19
836-851
2011
Homo sapiens (P42336)
brenda
Lannutti, B.J.; Meadows, S.A.; Herman, S.E.; Kashishian, A.; Steiner, B.; Johnson, A.J.; Byrd, J.C.; Tyner, J.W.; Loriaux, M.M.; Deininger, M.; Druker, B.J.; Puri, K.D.; Ulrich, R.G.; Giese, N.A.
CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability
Blood
117
591-594
2011
Homo sapiens (O00329)
brenda
Gao, M.; Wang, J.; Wang, W.; Liu, J.; Wong, C.W.
Phosphatidylinositol 3-kinase affects mitochondrial function in part through inducing peroxisome proliferator-activated receptor gamma coactivator-1beta expression
Br. J. Pharmacol.
162
1000-1008
2011
Homo sapiens
brenda
Zwaenepoel, O.; Tzenaki, N.; Vergetaki, A.; Makrigiannakis, A.; Vanhaesebroeck, B.; Papakonstanti, E.A.
Functional CSF-1 receptors are located at the nuclear envelope and activated via the p110delta isoform of PI 3-kinase
FASEB J.
26
691-706
2012
Mus musculus
brenda
Wu, Y.; Tan, H.; Shui, G.; Bauvy, C.; Huang, Q.; Wenk, M.; Ong, C.; Codogno, P.; Shen, H.
Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase
J. Biol. Chem.
285
10850-10861
2010
Homo sapiens, Mus musculus
brenda
Runyan, C.E.; Liu, Z.; Schnaper, H.W.
Phosphatidylinositol 3-kinase and Rab5 GTPase inversely regulate the Smad anchor for receptor activation (SARA) protein independently of transforming growth factor-beta1
J. Biol. Chem.
287
35815-35824
2012
Homo sapiens (P27986)
brenda
Fernandez-Acero, T.; Rodriguez-Escudero, I.; Vicente, F.; Monteiro, M.C.; Tormo, J.R.; Cantizani, J.; Molina, M.; Cid, V.J.
A yeast-based in vivo bioassay to screen for class I phosphatidylinositol 3-kinase specific inhibitors
J. Biomol. Screen.
17
1018-1029
2012
Homo sapiens (P42336)
brenda
Arancibia, S.; Benitez, D.; Nunez, L.; Jewell, C.; Langjahr, P.; Candia, E.; Zapata-Torres, G.; Cidlowski, J.; Gonzalez, M.; Hermoso, M.
Phosphatidylinositol 3-kinase interacts with the glucocorticoid receptor upon TLR2 activation
J. Cell. Mol. Med.
15
339-349
2011
Homo sapiens
brenda
Chen, Z.; Venkatesan, A.M.; Dehnhardt, C.M.; Ayral-Kaloustian, S.; Brooijmans, N.; Mallon, R.; Feldberg, L.; Hollander, I.; Lucas, J.; Yu, K.; Kong, F.; Mansour, T.S.
Synthesis and SAR of novel 4-morpholinopyrrolopyrimidine derivatives as potent phosphatidylinositol 3-kinase inhibitors
J. Med. Chem.
53
3169-3182
2010
Homo sapiens (P42336), Homo sapiens
brenda
Rewcastle, G.W.; Gamage, S.A.; Flanagan, J.U.; Frederick, R.; Denny, W.A.; Baguley, B.C.; Kestell, P.; Singh, R.; Kendall, J.D.; Marshall, E.S.; Lill, C.L.; Lee, W.J.; Kolekar, S.; Buchanan, C.M.; Jamieson, S.M.; Shepherd, P.R.
Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474)
J. Med. Chem.
54
7105-7126
2011
Homo sapiens (P48736), Homo sapiens
brenda
Smith, A.L.; DAngelo, N.D.; Bo, Y.Y.; Booker, S.K.; Cee, V.J.; Herberich, B.; Hong, F.T.; Jackson, C.L.; Lanman, B.A.; Liu, L.; Nishimura, N.; Pettus, L.H.; Reed, A.B.; Tadesse, S. et al.
Structure-based design of a novel series of potent, selective inhibitors of the class I phosphatidylinositol 3-kinases
J. Med. Chem.
55
5188-5219
2012
Homo sapiens (P42336), Homo sapiens (P48736)
brenda
Moir, L.M.; Trian, T.; Ge, Q.; Shepherd, P.R.; Burgess, J.K.; Oliver, B.G.; Black, J.L.
Phosphatidylinositol 3-kinase isoform-specific effects in airway mesenchymal cell function
J. Pharmacol. Exp. Ther.
337
557-566
2011
Homo sapiens
brenda
Kong, D.; Zhang, Y.; Yamori, T.; Duan, H.; Jin, M.
Inhibitory activity of flavonoids against class I phosphatidylinositol 3-kinase isoforms
Molecules
16
5159-5167
2011
Homo sapiens
brenda
Vantler, M.; Jesus, J.; Leppaenen, O.; Scherner, M.; Berghausen, E.M.; Mustafov, L.; Chen, X.; Kramer, T.; Zierden, M.; Gerhardt, M.; Ten Freyhaus, H.; Blaschke, F.; Sterner-Kock, A.; Baldus, S.; Zhao, J.J.; Rosenkranz, S.
Class IA phosphatidylinositol 3-kinase isoform p110alpha mediates vascular remodeling
Arterioscler. Thromb. Vasc. Biol.
35
1434-1444
2015
Rattus norvegicus, Rattus norvegicus (A0A0G2K344), Rattus norvegicus (Q9Z1L0), Homo sapiens (O00329), Homo sapiens (P42336), Homo sapiens (P42338), Homo sapiens, Mus musculus (O35904), Mus musculus (P42337), Mus musculus
brenda
Dickson, J.; Lee, W.; Shepherd, P.; Buchanan, C.
Enzyme activity effects of N-terminal His-tag attached to catalytic sub-unit of phosphoinositide-3-kinase
Biosci. Rep.
33
857-863
2013
Homo sapiens (P27986 AND P42336), Homo sapiens (P42338 AND O00329)
-
brenda
Gupta, V.K.; Rajala, A.; Rajala, R.V.
Non-canonical regulation of phosphatidylinositol 3-kinase gamma isoform activity in retinal rod photoreceptor cells
Cell Commun. Signal.
13
7-7
2015
Mus musculus (Q9JHG7)
brenda
Fernandez-Acero, T.; Rodriguez-Escudero, I.; Molina, M.; Cid, V.J.
The yeast cell wall integrity pathway signals from recycling endosomes upon elimination of phosphatidylinositol (4,5)-bisphosphate by mammalian phosphatidylinositol 3-kinase
Cell. Signal.
27
2272-2284
2015
Homo sapiens (P42336 AND P27986)
brenda
Watson, L.J.; Alexander, K.M.; Mohan, M.L.; Bowman, A.L.; Mangmool, S.; Xiao, K.; Naga Prasad, S.V.; Rockman, H.A.
Phosphorylation of Src by phosphoinositide 3-kinase regulates beta-adrenergic receptor-mediated EGFR transactivation
Cell. Signal.
28
1580-1592
2016
Homo sapiens (P48736)
brenda
Echeverria, I.; Liu, Y.; Gabelli, S.; Amzel, L.
Oncogenic mutations weaken the interactions that stabilize the p110?-p85? heterodimer in phosphatidylinositol 3-kinase ?.
FEBS J.
282
3528-3542
2015
Homo sapiens (P42336)
brenda
Thapa, N.; Choi, S.; Tan, X.; Wise, T.; Anderson, R.A.
Phosphatidylinositol phosphate 5-kinase Igamma and phosphoinositide 3-kinase/Akt signaling couple to promote oncogenic growth
J. Biol. Chem.
290
18843-18854
2015
Homo sapiens (P42336), Homo sapiens (P42338)
brenda
Somoza, J.R.; Koditek, D.; Villasenor, A.G.; Novikov, N.; Wong, M.H.; Liclican, A.; Xing, W.; Lagpacan, L.; Wang, R.; Schultz, B.E.; Papalia, G.A.; Samuel, D.; Lad, L.; McGrath, M.E.
Structural, biochemical, and biophysical characterization of idelalisib binding to phosphoinositide 3-kinase delta
J. Biol. Chem.
290
8439-8446
2015
Homo sapiens (O00329), Homo sapiens
brenda
Thomas, D.; Powell, J.A.; Green, B.D.; Barry, E.F.; Ma, Y.; Woodcock, J.; Fitter, S.; Zannettino, A.C.; Pitson, S.M.; Hughes, T.P.; Lopez, A.F.; Shepherd, P.R.; Wei, A.H.; Ekert, P.G.; Guthridge, M.A.
Protein kinase activity of phosphoinositide 3-kinase regulates cytokine-dependent cell survival
PLoS Biol.
11
e1001515
2013
Homo sapiens (P42336), Homo sapiens
brenda
Lacerda-Queiroz, N.; Brant, F.; Rodrigues, D.H.; Vago, J.P.; Rachid, M.A.; Sousa, L.P.; Teixeira, M.M.; Teixeira, A.L.
Phosphatidylinositol 3-kinase gamma is required for the development of experimental cerebral malaria
PLoS ONE
10
e0119633
2015
Mus musculus, Mus musculus C57BL/6
brenda
Li, D.; Yang, J.; Ma, H.; Sun, C.; Feng, R.
Inositol polyphosphate-4-phosphatase type II and rucaparib treatment inhibit the growth of osteosarcoma cells dependent on phosphoinositide 3-kinase/protein kinase B pathway
J. Cell. Biochem.
119
9899-9909
2018
Homo sapiens
brenda
Pridham, K.J.; Varghese, R.T.; Sheng, Z.
The role of class IA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunits in glioblastoma
Front. Oncol.
7
312
2017
Homo sapiens (P42336 AND P42338 AND P48736 AND O00329)
brenda
Bhattacharya, S.; McElhanon, K.E.; Gushchina, L.V.; Weisleder, N.
Role of phosphatidylinositol-4,5-bisphosphate 3-kinase signaling in vesicular trafficking
Life Sci.
167
39-45
2016
Homo sapiens (P42336 AND P42338 AND P48736 AND O00329)
brenda
Denorme, P.; Morren, M.A.; Hollants, S.; Spaepen, M.; Suaer, K.; Zutterman, N.; Labarque, V.; Legius, E.; Brems, H.
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum A brief report
Pediatr. Dermatol.
35
e186-e188
2018
Homo sapiens (P42336)
brenda