RAF/MAP kinase cascade PathwayStep5337 PathwayStep5336 PathwayStep5334 PathwayStep5335 RAS guanyl nucleotide exchange mediated by SOS1 bound to GRB2 in complex with phosphorylated ERBB4:ERBB2 heterodimers GRB2:SOS1 complex binds phosphorylated ERBB4:ERBB2 heterodimers RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and phosphorylated EGFR:ERBB2 heterodimers. GRB2:SOS1 complex binds phosphorylated EGFR:ERBB2 heterodimer GRB2 events in ERBB2 signaling Authored: Orlic-Milacic, M, 2011-11-04 ERBB2:EGFR and ERBB2:ERBB4 can directly recruit GRB2:SOS1 complex through phosphorylated C-tail tyrosines of EGFR (Y1068 and Y1086) and ERBB2 (Y1139) that serve as docking sites for GRB2 (Xie et al. 1995, Sepp-Lorenzino et al. 1996), which, again, results in SOS1-mediated guanyl-nucleotide exchange on RAS and activation of RAF and MAP kinases (Janes et al. 1994, Sepp-Lorenzino et al. 1996). Edited: D'Eustachio, P, 2011-11-07 Edited: Matthews, L, 2011-11-07 Reactome Database ID Release 431963640 Reactome, http://www.reactome.org ReactomeREACT_115854 Reviewed: Neckers, LM, 2011-11-11 Reviewed: Xu, W, 2011-11-11 PathwayStep3857