Activated MET receptor recruits the RAS guanyl nucleotide exchange factor (GEF) SOS1 indirectly, either through the GRB2 adapter (Ponzetto et al. 1994, Fournier et al. 1996, Shen and Novak 1997, Besser et al. 1997), GAB1 (Weidner et al. 1996) or SHC1 and GRB2 (Pelicci et al. 1995), or RANBP9 (Wang et al. 2002, Wang et al. 2004). Association of SOS1 with the activated MET receptor complex leads to exchange of GDP to GTP on RAS and activation of RAS signaling (Pelicci et al. 1995, Besser et al. 1997, Shen and Novak 1997, Wang et al. 2004).
PTPN11 (SHP2) may contribute to activation of RAS signaling downstream of MET (Schaeper et al. 2000, Furcht et al. 2014).
Sustained activation of MAPK1 (ERK2) and MAPK3 (ERK1) downstream of MET-activated RAS may require MET endocytosis and signaling from endosomes (Peschard et al. 2001, Hammond et al. 2001, Petrelli et al. 2002, Kermorgant and Parker 2008).
Binding of MET to MUC20 or RANBP10 interferes with RAS activation (Higuchi et al. 2004, Wang et al. 2004).