Upon receptor activation, Shc is recruited to the receptor complex, where it becomes tyrosine phosphorylated. The recruitment of Shc is mediated by Y593 (Y577 in the mature peptide) of the common beta chain (Bc), which binds the PTB domain of Shc (Pratt et al. 1996). Phosphorylated Shc interacts with Grb2 within a Grb2:Gab2 complex, promoting tyrosine phosphorylation of Gab2. The p85 subunit of PI3Kinases associates with phosphorylated Gab, and this induces activation of the catalytic p110 PI3K subunit leading to activation of Akt kinase, thereby regulating cell survival and/or proliferation.
Shoelson, SE, Sieff, CA, Pratt, JC, Ravichandran, KS, Burakoff, SJ, Weiss, M
Lord, JD, Moon, JJ, Neel, BG, Nelson, BH, Maeda, H, Yoakim, M, Gu, H
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