Human Epidermal Growth Factor Receptors EGFR, HER2, and HER3 (EGFR, HER2, HER3)

The **human epidermal growth factor receptor family (ErbB)** consists of four structurally related receptor tyrosine kinases: EGFR (also known as HER1), HER2, HER3, and HER4[1][2][6]. They share a general architecture of an extracellular ligand binding domain, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding (except for HER2, which is ligand-independent) induces homo- or hetero-dimerization, activating their kinase domain and initiating a phosphorylation cascade that drives cell proliferation, differentiation, and survival[1][2][6]. EGFR and HER2 are the most potent oncoproteins in the family, commonly overexpressed or mutated in numerous human cancers, and thus are major targets of antibody and small-molecule inhibitor therapies[1][2][7]. HER3, though catalytically impaired, functions as a crucial allosteric activator through heterodimerization with EGFR or HER2, amplifying oncogenic signaling[3][5]. Targeting these receptors has transformed cancer therapy, making them prototypes of "druggable" cell-surface oncogenic molecules.

Other names

HER1ErbB1c-erbB1ErbB2c-erbB2neu (in rodents)ErbB3c-erbB3

Inhibition of receptor dimerization and signaling (monoclonal antibodies block ligand binding or dimer formation) Inhibition of intracellular kinase activity (tyrosine kinase inhibitors block ATP binding or kinase activity of the cytoplasmic domain) Downregulation or degradation (some agents promote receptor internalization or degradation)