GRB2-1:SOS1 binds p-IRS1,p-IRS2

Stable Identifier
R-HSA-74736
Type
Reaction
Species
Homo sapiens
Compartment
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Inactive p21ras:GDP is anchored to the plasma membrane by a farnesyl residue. Insulin stimulation results in phosphorylation of IRS1/2 on tyrosine residues. GRB2 binds the phosphotyrosines via its SH2 domain. As IRS is phosphorylated by the insulin receptor near to the plasma membrane, the GRB2:SOS1:IRS interaction brings SOS1 and p21 Ras into close proximity.

Literature References
PubMed ID Title Journal Year
9003010 Roles of insulin receptor substrate-1 and Shc on insulin-like growth factor I receptor signaling in early passages of cultured human fibroblasts

Takahashi, Y, Tobe, K, Kadowaki, H, Katsumata, D, Fukushima, Y, Yazaki, Y, Akanuma, Y, Kadowaki, T

Endocrinology 1997
9832424 Differential regulation of insulin receptor substrate-2 and mitogen-activated protein kinase tyrosine phosphorylation by phosphatidylinositol 3-kinase inhibitors in SH-SY5Y human neuroblastoma cells

Kim, B, Leventhal, PS, White, MF, Feldman, EL

Endocrinology 1998
8316835 The function of GRB2 in linking the insulin receptor to Ras signaling pathways.

Skolnik, EY, Batzer, A, Li, N, Lee, CH, Lowenstein, E, Mohammadi, M, Margolis, B, Schlessinger, J

Science 1993
8810325 Interactions between Src homology SH2/SH3 adapter proteins and the guanylnucleotide exchange factor SOS are differentially regulated by insulin and epidermal growth factor.

Okada, S, Pessin, JE

J Biol Chem 1996
8621421 Systematic mapping of potential binding sites for Shc and Grb2 SH2 domains on insulin receptor substrate-1 and the receptors for insulin, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor

Ward, CW, Gough, KH, Rashke, M, Wan, SS, Tribbick, G, Wang, J

J. Biol. Chem. 1996
8530377 Substrate specificities of the insulin and insulin-like growth factor 1 receptor tyrosine kinase catalytic domains

Xu, B, Bird, VG, Miller, WT

J. Biol. Chem. 1995
9852124 Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling

Kim, B, Cheng, HL, Margolis, B, Feldman, EL

J. Biol. Chem. 1998
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