Ligand-induced activation of surface receptors, including the epidermal growth factor
receptor (EGFR), is followed by a desensitization process involving endocytosis and
receptor degradation. c-Cbl, a tyrosine phosphorylation substrate shared by several
signaling pathways, accelerates desensitization by recruiting EGFR and increasing receptor
polyubiquitination. Here we demonstrate that the RING type zinc finger of c-Cbl is essential
for ubiquitination and subsequent desensitization of EGFR. Mutagenesis of a single cysteine …