Reactome | PI3K binds to EGF:EGFR:GRB2:GAB1

PI3K binds to EGF:EGFR:GRB2:GAB1

Stable Identifier

R-HSA-177927

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

ReviewStatus

5/5

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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
11606067	Unique phosphorylation mechanism of Gab1 using PI 3-kinase as an adaptor protein Fukushima, Y, Inukai, K, Kikuchi, M, Ogihara, T, Onishi-Haraikawa, Y, Asano, T, Funaki, M, Sakoda, H, Anai, M, Katagiri, H, Shibuya, M, Gotoh, N, Oka, Y, Ono, H	Biochem Biophys Res Commun	2001
10648629	A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling Falasca, M, Rodrigues, GA, Schlessinger, J, Ong, SH, Zhang, Z	Mol Cell Biol	2000