Degradation of the GAB1 adaptor by the ubiquitin-proteasome pathway hampers HGF/SF-MET signaling

► Upon hepatocyte growth factor/scatter factor (HGF/SF) induced MET tyrosine kinase receptor activation, the GAB1 adaptor is degraded by the proteasome. ► GAB1 is recruited by the activated MET receptor which in turn induces GAB1 ubiquitination. ► GAB1 is ubiquitinated in a CBL-dependent manner. ► Ligand-induced GAB1 degradation hampers downstream activation of ERK MAP kinases upon MET rechallenge. ► Down-regulation of GAB1 is a negative feedback mechanism in HGF/SF-MET signaling.