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).
Woscholski, R, Waterfield, MD, Ahmadi, K, Leevers, SJ, Vanhaesebroeck, B, Timms, J, Parker, PJ, Driscoll, PC, Katso, R
Koyasu, S
Sun, J, Pedersen, M, Rönnstrand, L
1-phosphatidylinositol-3-kinase activity of PI3K:p-KIT:sSCF dimer:p-KIT,PI3K:p(Y)-GAB2:GRB2:p-SHP2:p-KIT complex [plasma membrane]
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