CBL ubiquitinates FRS2 and FGFR Authored: Rothfels, K, 2011-08-15 EC Number: 6.3.2.19 Grb2 bound to tyrosine phosphorylated FRS2 forms a ternary complex with Cbl through the binding of the SH3 domains of Grb2 to a proline rich region in Cbl. Grb2-mediated recruitment of Cbl results in ubiquitination of FGFR and FRS2. Cbl is a multidomain protein that posses an intrinsic ubiquitin ligase activity and also functions as a platform for recruitment of a variety of signaling proteins. Multiple mechanisms appear to be required for downregulation of FGFR, as internalization of the receptor is reduced but not abolished if recruitment of CBL to FRS2 is compromised by mutation of GRB2-binding sites. Pubmed11997436 Pubmed12815057 Reactome Database ID Release 431270444 Reactome, http://www.reactome.org ReactomeREACT_111231 Reviewed: Gotoh, N, 2011-08-26 Ub-Activated FGFR complex:Ub-p-FRS2alpha Activated FGFR:p-FRS2alpha:p-CBL:GRB2 ubiquitin