Receptor tyrosine-protein kinase erbB family member (ErbB (or HER, depending on context and specific member))

The receptor tyrosine-protein kinase erbB family comprises four closely related single-pass transmembrane proteins—epidermal growth factor receptor (EGFR, also known as ErbB1 or HER1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4)—that function as cell surface receptors for various peptide growth factors. Each consists of an extracellular ligand-binding domain subdivided into four subdomains involved in ligand recognition and dimerization; a single transmembrane helix; and an intracellular region containing a protein tyrosine kinase domain responsible for signal propagation via phosphorylation events. Ligand binding induces homo-/heterodimerization among these receptors, activating downstream signaling cascades such as PI3K/Akt and Ras/MAPK pathways that regulate cell proliferation, survival, differentiation, motility, and apoptosis. Aberrant activation through overexpression or mutation is implicated in numerous human malignancies—including breast cancer (especially HER2-positive subtypes), non-small cell lung cancer (NSCLC) driven by EGFR mutations/amplification—and has made these receptors major therapeutic targets. Multiple small-molecule inhibitors target their intracellular kinases while monoclonal antibodies block extracellular domains to prevent activation. Resistance to therapy remains a significant clinical challenge.

Other names

Epidermal growth factor receptor familyEGFR familyHER familyErbB1 (EGFR)ErbB2 (HER2/neu)ErbB3 (HER3)ErbB4 (HER4)

– Inhibition of tyrosine kinase activity by small molecules targeting the ATP-binding site – Blockade of ligand binding or dimerization by monoclonal antibodies targeting the extracellular domain