PathwayStep4136 PathwayStep4138 PathwayStep4137 PathwayStep4150 Activated ERK1/2 threonine-phosphorylate FRS2alpha. p-CBL:GRB2 binds p-FRS2alpha:activated FGFR CBL ubiquitinates FRS2 and FGFR Negative regulation of FGFR signaling Authored: Rothfels, K, 2011-08-15 Once activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-mediated inhibition of FRS2-tyrosine phosphorylation and the attenuation of ERK signaling through the action of dual-specificity phosphatases, IL17RD/SEF, Sprouty and Spred proteins. A number of these inhibitors are themselves transcriptional targets of the activated FGFR pathway. Pubmed11997436 Pubmed12815057 Pubmed18452557 Pubmed20940169 Reactome Database ID Release 431270470 Reactome, http://www.reactome.org ReactomeREACT_111184 Reviewed: Gotoh, N, 2011-08-26 Spry regulation of FGF signaling