PathwayStep4110 PathwayStep4111 PathwayStep4112 PathwayStep4113 PathwayStep4114 PathwayStep4117 PathwayStep4116 PathwayStep4115 Phosphorylation of FRS2-alpha by activated FGFR Activated FGFR binds FRS2beta Activated FGFR and FRS2 bind to SHP2 Phosphorylation of FRS2-beta by activated FGFR GRB2:SOS1 binds to p-FRS2:activated FGFR SHP2 is phosphorylated by activated FGFR Ras nucleotide exchange by GRB2:SOS1 bound to p-FRS2:activated FGFR Activated FGFR binds FRS2alpha FRS2-mediated cascade Authored: de Bono, B, 2007-01-10 10:27:18 Edited: Jupe, S, 2010-02-03 Pubmed10377388 Pubmed11447289 Pubmed15863030 Pubmed16682955 Pubmed18452557 Pubmed9182757 Reactome Database ID Release 43190345 Reactome, http://www.reactome.org ReactomeREACT_21247 Reviewed: Gotoh, N, 2011-08-26 Reviewed: Mohammadi, M, 2007-02-06 21:44:35 The FRS family of scaffolding adaptor proteins has two members, FRS2alpha and FRS2beta (also known as FRS3 or SNT-2). Activation of FGFR tyrosine kinase allows FRS2 proteins to become phosphorylated on tyrosine residues and then bind to the adaptor GRB2 and the tyrosine phosphatase SHP2. Subsequently, SHP2 activates the RAS-MAP kinase pathway and GRB2 activates the RAS-MAP kinase , PI-3-kinase and ubiquitinations/degradation pathways by binding to SOS, GAB1 and CBL, respectively, via the SH3 domains of GRB2. FRS2alpha acts as a central mediator in FGF signaling mainly because it induces sustained levels of activation of ERK with ubiquitous expression.<br><br><br> RAF/MAP kinase cascade PathwayStep3857