The ErbB2 (HER2) proto-oncogene encodes a 185 kDa transmembrane, receptor-like glycoprotein with intrinsic tyrosine kinase activity. ErbB2 is a key therapeutic target in the treatment of breast cancer and other carcinomas and targeting the regulation of ErbB2 degradation by the c-Cbl-regulated proteolytic pathway is one potential therapeutic strategy. A number of cytoplasmic signaling molecules are thought to mediate mitogenic signaling from the activated ErbB2 oncoprotein through binding to phospho-tyrosine residues located within the intracellular portion of the ErbB2 molecule, including Grb2, PLCg, c-Src, Ras-GAP, SHC and Grb7.
