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.
Carlberg, M, Thömmes, K, Lennartsson, J, Rönnstrand, L
Lanfrancone, L, Dentelli, P, Pegoraro, L, Pelicci, PG, Rosso, A, Brizzi, MF
Roskoski, R Jr
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