Activated FGFR2:p-FRS2:GRB2:GAB1:PI3KR1 binds PIK3CA

Stable Identifier
R-HSA-5654614
Type
Reaction [binding]
Species
Homo sapiens
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The Src homology 2 (SH2) domain of the phosphatidylinositol 3-kinase (PIK3) regulatory subunit (PIK3R1, i.e. PI3Kp85) binds to GAB1 in a phosphorylation-independent manner. GAB1 serves as a docking protein which recruits a number of downstream signalling proteins. PIK3R1 can bind to either GAB1 or phosphorylated GAB1(Rodrigues et al. 2000, Onishi-Haraikawa et al. 2001). 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 (Mandelker et al. 2009, Burke et al. 2011).

Literature References
PubMed ID Title Journal Year
15863030 Cellular signaling by fibroblast growth factor receptors

Eswarakumar, VP, Lax, I, Schlessinger, J

Cytokine Growth Factor Rev 2005
11353842 Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins

Ong, SH, Hadari, YR, Gotoh, N, Guy, GR, Schlessinger, J, Lax, I

Proc Natl Acad Sci U S A 2001
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