PI3K-containing complexes phosphorylate PIP2 to PIP3

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R-HSA-109699
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Reaction [transition]
Species
Homo sapiens
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PI3K can be activated downstream of receptor tyrosine kinases (RTKs) such as insulin receptor IGF1R (Hadari et al. 1992, Kooijman et al. 1995). In unstimulated cells, PI3K class IA exists as an inactive heterodimer of a p85 regulatory subunit (encoded by PIK3R1, PIK3R2 or PIK3R3) and a p110 catalytic subunit (encoded by PIK3CA, PIK3CB or PIK3CD). Binding of the iSH2 domain of the p85 regulatory subunit to the ABD and C2 domains of the p110 catalytic subunit both stabilizes p110 and inhibits its catalytic activity. This inhibition is relieved when the SH2 domains of p85 bind phosphorylated tyrosines on activated RTKs or their adaptor proteins. Binding to membrane-associated receptors brings activated PI3K in proximity to its membrane-localized substrate, PIP2, facilitating phosphorylation (Mandelker et al. 2009, Burke et al. 2011; reviewed in Koyasu et al, 2003; Engelman et al, 2006).

Literature References
PubMed ID Title Journal Year
21827948 Dynamics of the phosphoinositide 3-kinase p110? interaction with p85? and membranes reveals aspects of regulation distinct from p110?

Burke, JE, Vadas, O, Berndt, A, Finegan, T, Perisic, O, Williams, RL

Structure 2011
7543144 Insulin-like growth factor induces phosphorylation of immunoreactive insulin receptor substrate and its association with phosphatidylinositol-3 kinase in human thymocytes

Kooijman, R, Lauf, JJ, Kappers, AC, Rijkers, GT

J. Exp. Med. 1995
1381348 Insulin and insulinomimetic agents induce activation of phosphatidylinositol 3'-kinase upon its association with pp185 (IRS-1) in intact rat livers

Hadari, YR, Tzahar, E, Nadiv, O, Rothenberg, P, Roberts, CT, LeRoith, D, Yarden, Y, Zick, Y

J. Biol. Chem. 1992
19805105 A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane

Mandelker, D, Gabelli, SB, Schmidt-Kittler, O, Zhu, J, Cheong, I, Huang, CH, Kinzler, KW, Vogelstein, B, Amzel, LM

Proc. Natl. Acad. Sci. U.S.A. 2009
16847462 The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism

Engelman, JA, Luo, J, Cantley, LC

Nat. Rev. Genet. 2006
12660731 The role of PI3K in immune cells

Koyasu, S

Nat Immunol 2003
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Catalyst Activity
Title
1-phosphatidylinositol-3-kinase activity of PI3K-containing complexes [cytosol]
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