Receptor tyrosine-protein kinase erbB-2, extracellular domain II (HER2 (also known as ERBB2))

HER2 (encoded by the ERBB2 gene) is a plasma membrane-bound receptor tyrosine kinase of the EGFR family comprising four main domains: an extracellular domain (ECD) composed of four subdomains (I–IV), a single transmembrane domain, a juxtamembrane region, and an intracellular kinase domain. The extracellular domain II of HER2 is crucial for mediating receptor dimerization, a key event in the activation of signaling pathways that promote cell proliferation and survival. Unlike other EGFR family members, HER2 does not bind ligand but acts as a preferred dimerization partner. Overexpression or mutation leads to aberrant, ligand-independent dimerization and signaling, driving oncogenesis in breast, gastric, and other cancers. Therapeutics such as pertuzumab specifically target domain II to inhibit dimerization, while trastuzumab binds to domain IV. HER2 is an established cancer biomarker and a major target for monoclonal antibodies and tyrosine kinase inhibitors[1][2][4][5][6].

Other names

HER2ErbB-2NEUCD340HER-2/neuc-erbB-2ERBB2

Inhibition of HER2 dimerization and signaling (e.g., trastuzumab binds to domain IV, pertuzumab to domain II), Antibody-dependent cellular cytotoxicity (ADCC), Inhibition of receptor phosphorylation and downstream signaling (e.g., by small molecule tyrosine kinase inhibitors), Disruption of hetero- and homodimer formation with other ErbB family receptors