Reactome | Synthesis of PIP3 from PIP2 by PI3K

Synthesis of PIP3 from PIP2 by PI3K

Stable Identifier

R-HSA-1433514

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

ReviewStatus

5/5

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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