Epidermal growth factor receptor, Receptor tyrosine-protein kinase ErbB-2, Receptor tyrosine-protein kinase ErbB-4 (EGFR, HER2, HER4)

The ErbB family of receptor tyrosine kinases—including epidermal growth factor receptor (EGFR/HER1/ErbB-1), receptor tyrosine-protein kinase ErbB-2 (HER2/neu), and receptor tyrosine-protein kinase ErbB-4 (HER4)—are single-pass transmembrane proteins characterized by extracellular ligand-binding, a single transmembrane region, and an intracellular tyrosine kinase domain[1][5][7]. Activation by ligand binding (except for ERBB2, which lacks a known direct ligand) promotes dimerization, autophosphorylation, and activation of downstream signaling pathways including MAPK and PI3K, leading to effects on cell proliferation, survival, and differentiation[3][7][4]. These receptors are frequently dysregulated in cancer through mutations, amplifications, fusions, or overexpression, and are key therapeutic targets in several malignancies. Multiple targeted therapies—including kinase inhibitors and monoclonal antibodies—have been developed to inhibit their function in disease[2][3][7].

Other names

HER1ErbB-1HER2neuHER4

Competitive inhibition of ATP binding (small molecule tyrosine kinase inhibitors, e.g., gefitinib, lapatinib, afatinib); Ligand blocking/antibody-mediated inhibition of dimerization or signaling (e.g., trastuzumab for ERBB2/HER2, cetuximab for EGFR); Antibody-drug conjugate delivery (e.g., T-DM1)