GRB2:SOS interacts with p-KIT

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.

GRB2（生长因子受体结合蛋白2）是一种单SH2结构域和双SH3结构域的适配蛋白。它部分存在于与RAS GDP/GTP交换因子SOS预形成的复合体中。GRB2的SH2结构域能够直接与自磷酸化位点Y703和Y936上的激活型KIT结合（Thommes等，1999年）。此外，GRB2还可以通过结合KIT下游信号转导分子如SHP2、SHC1、GAB1和GAB2等间接招募至KIT（Rönnstrand，2004年，Linnekin，1999年）。GRB2与SOS复合体结合KIT后，可激活小GTP酶蛋白RAS。值得注意的是，并非所有GRB2与KIT的相互作用均涉及RAS的激活；GRB2亦能作为适配蛋白，招募GAB2（Sun等，2008年）和CBL（Sun等，2007年）至KIT。