Reactome | GRB2:SOS interacts with p-KIT

GRB2:SOS interacts with p-KIT

Stable Identifier

R-HSA-205286

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

ReviewStatus

5/5

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GRB2 is an adapter protein with one SH2 domain and two SH3 domains. It exists in part as a preformed complex with the RAS GDP/GTP exchanger SOS. GRB2 with its SH2 domain binds directly to activated KIT on autophosphorylated sites Y703 and Y936 (Thommes et al. 1999). GRB2 can also be recruited indirectly to KIT by binding KIT downstream signal transduction molecules such as SHP 2, SHC1, GAB1 and GAB2 (Rönnstrand 2004, Linnekin 1999). GRB2:SOS complex bound to KIT then activates the small GTPase protein RAS. It should be noted that not all GRB2 interactions with KIT involve an activation of RAS; GRB2 can also act as an adapter protein for recruiting both GAB2 (Sun et al. 2008) and CBL (Sun et al. 2007) to KIT.

Literature References

PubMed ID	Title	Journal	Year
10377264	Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor Thömmes, K, Lennartsson, J, Carlberg, M, Rönnstrand, L	Biochem J	1999
8950973	Discrete protein interactions with the Grb2/c-Cbl complex in SCF- and TPO-mediated myeloid cell proliferation Brizzi, MF, Dentelli, P, Lanfrancone, L, Rosso, A, Pelicci, PG, Pegoraro, L	Oncogene	1996
16129412	Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor Roskoski, R Jr	Biochem Biophys Res Commun	2005