GRB2 binds SOS1 GRB2:SOS1 complex binds to EGF:EGFR complex SOS1-mediated nucleotide exchange of RAS (EGF:EGFR:GRB2:SOS1) RAF/MAP kinase cascade GRB2 events in EGFR signaling Authored: Castagnoli, L, 2006-10-10 13:09:34 Autophosphorylated EGFR tyrosine residues are docking sites for many downstream effectors in EGFR signaling. The adaptor protein GRB2 binds to phosphotyrosine residues in the C-tail of EGFR through its SH2 domain. GRB2 is constitutively associated with SOS, a guanine nucleotide exchange factor of RAS. GRB2 binding to phosphorylated EGFR results in the recruitment of SOS to the plasma membrane where it comes in proximity to RAS. This mechanism has been seen to be the model for RAS activation. Pubmed11498013 Pubmed11706405 Reactome Database ID Release 43179812 Reactome, http://www.reactome.org ReactomeREACT_12606 Reviewed: Heldin, CH, 2008-02-12 09:44:02 PathwayStep3857 PathwayStep3843 PathwayStep3844 PathwayStep3845