GRB2:SOS interacts with p-KIT

Stable Identifier
R-HSA-205286
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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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 involves an activation of RAS, but it 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
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
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
16129412 Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor

Roskoski, R Jr

Biochem Biophys Res Commun 2005
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