Reactome | Recruitment of GRB2:SOS to p-5Y-LAT

Recruitment of GRB2:SOS to p-5Y-LAT

Stable Identifier

R-HSA-2396599

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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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). Following phosphorylation of LAT, the GRB2:SOS complex binds to the phosphorylated tyrosines and is thereby translocated to the inner face of the plasma membrane where inactive RAS:GDP resides. The three distal tyrosines, Y171, Y191 and Y226 of LAT are responsible for GRB2 association (Balagopalan et al. 2010, Zhang et al. 2000).

Literature References

PubMed ID	Title	Journal	Year
10811803	Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling. Zhang, W, Trible, RP, Zhu, M, Liu, SK, McGlade, CJ, Samelson, LE	J Biol Chem	2000
8663278	Syk-dependent phosphorylation of Shc. A potential link between FcepsilonRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2 Jabril-Cuenod, B, Zhang, C, Scharenberg, AM, Paolini, R, Numerof, R, Beaven, MA, Kinet, JP	J. Biol. Chem.	1996