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ERBB3

Erb-b2 receptor tyrosine kinase 3 (ERBB3), also known as HER3, is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This protein contains a neuregulin binding domain but not an active kinase domain. However, it enables to bind this ligand but not convey the signal into the cell via protein phosphorylation, and produces heterodimers with other EGF receptor family members which do have kinase activity.
Generally, ERBB3 is co-expressed with other RTKs in cancer cells. It primarily enhances tumor initiation and progression by activation of the oncogenic PI-3 K/Akt signaling. Due to its role in therapeutic resistance, the ERBB3/PI-3 K/Akt pathway is the main cause of treatment failure in cancer therapy. Besides, ERBB3 serves an essential role in the development of a variety of human cancers, such as platinum-resistant/refractory ovarian cancer, erbB2-overexpressing (erbB2+) breast cancer, EGFR tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC), as well as castration-resistant prostate cancer (CRPC). At present, a number of anti-ERBB3 monoclonal Abs that prevent ligand-induced activation of erbB3 have displayed significant antitumor activity in vitro and in vivo, for example, U3-1287/AMG 888 (Amgen Inc., Thousand Oaks, CA), MM-121 and MM-111 (Merrimack Pharmaceuticals, Cambridge, MA).
Gene ID: 2065
UniProt ID: P21860