Reactome | Interaction of GRB2:SOS complex with p-SHC1

Interaction of GRB2:SOS complex with p-SHC1

Stable Identifier

R-HSA-2730844

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Interaction of GRB2:SOS complex with p-SHC1

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GRB2 is an adapter protein that contains a central SH2 domain flanked by N- and C-terminal SH3 domains. GRB2 acts downstream of receptor protein-tyrosine kinases and is involved in Ras and MAP kinase pathway activation by associating with the guanine exchange factor (GEF) SOS. GRB2 is constitutively bound to SOS through its SH3 domains, which interact with a proline-rich sequence in the C-terminal part of SOS (Chardin et al. 1993). GRB2-SOS complex binds to phosphotyrosine Y239 and Y317 of SHC1. SHC1 associates with the tyrosine-phosphorylated ITAMs of the FCERI beta-chain and can recruit SOS to membrane. SHC1 and SOS have also been described to associate with LAT via GRB2. Shc binding to Phospho-ITAMs (in vitro binding to phospho peptides) has never been linked to any biological function (activation) and is probably not relevant in a physiological setting.

Literature References

PubMed ID	Title	Journal	Year
19909365	Adapters in the organization of mast cell signaling Lessmann, E, Rivera, J, Alvarez-Errico, D	Immunol. Rev.	2009
9199344	Shc contains two Grb2 binding sites needed for efficient formation of complexes with SOS in B lymphocytes Harmer, SL, DeFranco, AL	Mol Cell Biol	1997
8493579	Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2 Gale, NW, Camonis, JH, Chardin, P, Schlessinger, J, Wigler, MH, Bar-Sagi, D, Van Aelst, L	Science	1993