Synthesis of PIP3 from PIP2 by PI3K

Stable Identifier
Reaction [transition]
Homo sapiens
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PI3 kinases catalyze the production of phosphatidylinositol-3, 4, 5-triphosphate (PIP3) by phosphorylating phosphatidylinositol-4, 5-bisphosphate (PIP2). PIP3 bound to the inner lipid bilayer of the plasma membrane promotes the recruitment and activation of AKT. Active AKT subsequently phosphorylates the pro-apoptotic factor BAD at Ser136. Phosphorylated BAD binds 14-3-3 proteins, sequestering BAD from interaction with the anti-apoptotic molecule BCL-XL and leaving BCL-Xl free to inhibit BAX-triggered apoptosis. In this way, AKT-mediated BAD phosphorylation promotes cell survival. The alternative route for c-Kit mediated survival is through AKT-mediated phosphorylation and inactivation of the forkhead transcription factor (FoxO3a) (Engstrom et al, 2003; Lennartson et al, 2005).

Literature References
PubMed ID Title Journal Year
11395417 Synthesis and function of 3-phosphorylated inositol lipids

Woscholski, R, Waterfield, MD, Ahmadi, K, Leevers, SJ, Vanhaesebroeck, B, Timms, J, Parker, PJ, Driscoll, PC, Katso, R

Annu Rev Biochem 2001
12660731 The role of PI3K in immune cells

Koyasu, S

Nat Immunol 2003
18697750 Gab2 is involved in differential phosphoinositide 3-kinase signaling by two splice forms of c-Kit

Sun, J, Pedersen, M, Rönnstrand, L

J Biol Chem 2008
Catalyst Activity

phosphatidylinositol 3-kinase activity of PI3K:p-KIT:sSCF dimer:p-KIT,PI3K:p(Y)-GAB2:GRB2:p-SHP2:p-KIT complex [plasma membrane]

Orthologous Events
Cross References
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