ErbB family receptor tyrosine kinase (ErbB)

The **ErbB family receptor tyrosine kinases** are a group of four closely related single-pass transmembrane proteins that function as key regulators in cell signaling. The four members—epidermal growth factor receptor (**EGFR**, also called **ErbB1** or **HER1**), **ErbB2** (**HER2**, neu), **ErbB3** (**HER3**), and **ErbB4** (**HER4**)—share a common structure consisting of an extracellular ligand-binding domain made up of four subdomains, a single transmembrane helix, and an intracellular region containing a protein tyrosine kinase domain. Upon binding specific ligands such as epidermal growth factors, these receptors dimerize to form either homodimers or heterodimers. Dimerization activates their intrinsic kinase activity leading to autophosphorylation on specific tyrosines within their cytoplasmic tails. This triggers multiple downstream signaling pathways that regulate essential cellular processes including proliferation, survival, differentiation, migration—and when dysregulated—can drive oncogenesis. The clinical significance is underscored by frequent overexpression/mutation/amplification in various cancers; this has led to development and approval of several targeted therapies against individual members such as trastuzumab for breast cancers overexpressing HER2/neu. The complexity arises from both redundancy among family members and unique roles each plays during development; null mutations are embryonically lethal while aberrant activation is implicated in many human malignancies[1][3][4].

Other names

Epidermal growth factor receptor familyHER family (Human Epidermal growth factor Receptor)EGFR familyErbB1 (EGFR, HER1)ErbB2 (HER2, neu)ErbB3 (HER3)ErbB4 (HER4)

Drugs act by one or more of the following mechanisms— - Inhibition of ligand binding to the extracellular domain of the receptor - Inhibition of dimerization or oligomerization required for activation - Inhibition of intracellular tyrosine kinase activity - Induction of antibody-dependent cellular cytotoxicity