RAF/MAP kinase cascade PathwayStep5373 PathwayStep5375 PathwayStep5374 PathwayStep5376 Recruitment of GRB2:SOS1 to phosphorylated SHC1 in complex with phosphorylated ERBB4 homodimers RAS guanyl-nucleotide exchange mediated by SOS1 in complex with GRB2 and p-Y349,350-SHC1:p-ERBB4 SHC1 binds P-ERBB4 isoform dimers Phosphorylation of SHC1 by ERBB4 homodimers SHC1 events in ERBB4 signaling All splicing isoforms of ERBB4 possess two tyrosine residues in the C-tail that serve as docking sites for SHC1 (Kaushansky et al. 2008, Pinkas-Kramarski et al. 1996, Cohen et al. 1996). Once bound to ERBB4, SHC1 becomes phosphorylated on tyrosine residues by the tyrosine kinase activity of ERBB4, which enables it to recruit the complex of GRB2 and SOS1, resulting in the guanyl-nucleotide exchange on RAS and activation of RAF and MAP kinase cascade (Kainulainen et al. 2000). Authored: Orlic-Milacic, M, 2011-11-04 Edited: Matthews, L, 2011-11-07 Reactome Database ID Release 431250347 Reactome, http://www.reactome.org ReactomeREACT_116005 Reviewed: Earp HS, 3rd, 2012-02-20 Reviewed: Harris, RC, 2011-11-11 Reviewed: Misior, AM, 2012-02-20 Reviewed: Zeng, F, 2011-11-11 PathwayStep3857