Reactome | PI3K associates with phosphorylated GAB2

PI3K associates with phosphorylated GAB2

Stable Identifier

R-HSA-2730842

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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PI3K associates with phosphorylated GAB2

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Phosphorylated Y452, Y476, and Y584 of GAB2 binds p85 regulatory subunit of PI3K kinase, resulting in activation of PI3K pathway. PI3K is required for mast cell degranulation and anaphylaxis response but not for cytokine production or contact hypersensitivity (Nishida et al. 2011). Activated PI3K generates second messenger PtdInsP3 (PIP3) at the inner membrane, which provides docking sites for pleckstrin homology (PH) domains of PDK1, AKT and BTK. Activated AKT controls major downstream targets like mTORC1, FOXO3 and GSK3beta pathways that regulate mast cell growth, homeostasis, and cytokine production. BTK triggers PLCgamma2 activation, thereby inducing activation of the transcription factor NFAT and NF-kB.

Literature References

PubMed ID	Title	Journal	Year
10068651	Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors Hirano, T, Ishihara, K, Itoh, M, Fukada, T, Yoshida, Y, Hibi, M, Shirogane, T, Takahashi-Tezuka, M, Nishida, K, Atsumi, T, Ohtani, T	Blood	1999
16456001	Scaffolding adapter Grb2-associated binder 2 requires Syk to transmit signals from FcepsilonRI Gu, H, Lowell, CA, Yu, M, Neel, BG	J. Immunol.	2006
21653832	Gab2, via PI-3K, regulates ARF1 in Fc?RI-mediated granule translocation and mast cell degranulation Koseki, H, Hasegawa, A, Hirano, T, Nishida, K, Iwamatsu, A, Yamasaki, S	J. Immunol.	2011