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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Synthesis of PIP3 from PIP2 by PI3K
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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

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

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
Participants
Input
Output
Participates
as an event of
Catalyst Activity

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]

Physical Entity
PI3K:p-KIT:sSCF dimer:p-KIT,PI3K:p(Y)-GAB2:GRB2:p-SHP2:p-KIT complex [plasma membrane] (Homo sapiens)
Activity
1-phosphatidylinositol-3-kinase activity (GO:0016303)
Orthologous Events
Synthesis of PIP3 from PIP2 by PI3K (Bos taurus)
Synthesis of PIP3 from PIP2 by PI3K (Caenorhabditis elegans)
Synthesis of PIP3 from PIP2 by PI3K (Canis familiaris)
Synthesis of PIP3 from PIP2 by PI3K (Danio rerio)
Synthesis of PIP3 from PIP2 by PI3K (Gallus gallus)
Synthesis of PIP3 from PIP2 by PI3K (Mus musculus)
Synthesis of PIP3 from PIP2 by PI3K (Rattus norvegicus)
Synthesis of PIP3 from PIP2 by PI3K (Sus scrofa)
Synthesis of PIP3 from PIP2 by PI3K (Xenopus tropicalis)
Cross References
Rhea
Authored
Garapati, P V  (2011-07-11)
Reviewed
Rönnstrand, L  (2011-08-22)
Created
Garapati, P V  (2011-07-11)
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