p-CBL:GRB2 binds p-FRS2alpha:activated FGFR Authored: Rothfels, K, 2011-08-15 Pubmed11997436 Reactome Database ID Release 431270439 Reactome, http://www.reactome.org ReactomeREACT_111145 Reviewed: Gotoh, N, 2011-08-26 The ubiquitin ligase CBL exists in a complex with GRB2 and is recruited to tyrosine-phosphorylated FRS2 after FGF stimulation. In addition to promoting the ubiquitination, endocytosis, and degradation of the activated receptor complex, recruitment of the p-CBL:GRB2 complex seems to attenuate FGFR signaling by competing with GRB2:SOS1 for binding to the direct GRB2-binding sites on p-FRS2. Activated FGFR:p-FRS2-alpha:p-SHP2 Phospho-CBL:GRB2 Activated FGFR:p-FRS2alpha:p-CBL:GRB2