Epidermal growth factor receptor (HER1); Human epidermal growth factor receptor 2 (HER2); Human epidermal growth factor receptor 4 (HER4) (EGFR (HER1); HER2; HER4)

Epidermal growth factor receptor family members HER1 (EGFR), HER2, and HER4 are single-pass transmembrane receptor tyrosine kinases crucial for the regulation of cell proliferation, differentiation, and survival. Activation occurs via ligand-induced dimerization (except HER2, which has no direct ligand), leading to autophosphorylation and downstream signaling. Dysregulation, particularly overexpression or gene amplification, plays a pivotal role in several cancers, making these receptors important therapeutic targets. They share similar protein domains (extracellular ligand-binding, transmembrane, and cytoplasmic kinase domains), but differ in ligand specificity and downstream effects. HER2 is unique in always being poised for dimerization, often forming heterodimers with other HER family members.

Other names

EGFRErbB1ErbB2neu (in rodents)ErbB4

Antibody-based inhibition (e.g., trastuzumab blocks HER2 dimerization); Tyrosine kinase inhibition (e.g., lapatinib for HER2, gefitinib for EGFR/HER1); Downregulation of receptor expression; Prevention of ligand binding or dimerization; Antibody-dependent cellular cytotoxicity (ADCC, for some anti-HER2 mAbs)