description
All ERBB2 heterodimers, ERBB2:EGFR, ERBB2:ERBB3 and ERBB2:ERBB4, are able to activate RAF/MAP kinase cascade by recruiting SHC1 (Pinkas-Kramarski et al. 1996, Sepp-Lorenzino et al. 1996) to phosphorylated C-tail tyrosine residues in either EGFR (Y1148 and Y1173), ERBB2 (Y1196, Y1221, Y1222 and Y1248), ERBB3 (Y1328) or ERBB4 (Y1188 and Y1242 in JM-A CYT1 isoform, Y1178 and Y1232 in JM-B CYT1 isoform, Y1172 and Y1226 in JM-A CYT2 isoform). SHC1 recruitment is followed by phosphorylation (Segatto et al. 1993, Soler et al. 1994), and the phosphorylated SHC1 recruits GRB2:SOS1 complex (Xie et al. 1995), which leads to SOS1-mediated guanyl-nucleotide exchange on RAS (Xie et al. 1995) and downstream activation of RAF and MAP kinases

external resources
NCBI:1269490
REACTOME:R-HSA-1250196

genes
BTC , HBEGF , EGF , EGFR , ERBB2 , ERBB3 , ERBB4 , EREG , GRB2 , NRG1 , HRAS , KRAS , NRAS , PRKCA , PRKCD , PRKCE , PTPN12 , SHC1 , SOS1 , NRG2 , NRG3 , NRG4 ,