ErbB family receptor tyrosine-protein kinase (ErbB (or HER/EGFR family, with individual members abbreviated as EGFR/ErbB1/HER1, HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4))

The **ErbB family** comprises four closely related **receptor tyrosine kinases** found on the cell surface: **epidermal growth factor receptor** (**EGFR**, also known as Her1 or ErbB1), **Her2** (**ErbB2**, neu), **Her3** (**ErbB3**) and **Her4** (**ErbB4**) in humans. These proteins share a common structure featuring an extracellular ligand-binding domain composed of four subdomains involved in ligand recognition and dimerization; a single transmembrane helix; and an intracellular region containing a juxtamembrane segment followed by a protein kinase domain responsible for autophosphorylation upon activation. Ligand binding induces conformational changes that promote homo-/heterodimerization among these receptors—most notably between Her3's impaired catalytic site and Her2's lack of direct ligand binding—which triggers downstream signaling cascades including RAS/MAPK, PI3K/Akt, PLCγ-PKC pathways. These pathways regulate key cellular processes such as proliferation, survival/apoptosis inhibition, migration/invasion/metastasis potential. Aberrant expression/mutation within this gene family is strongly implicated across multiple human cancers—including lung adenocarcinoma (~15% have activating EGFR mutations), breast carcinoma (~20% are HER2-amplified), colorectal carcinoma—and targeted therapies have been developed accordingly. However resistance frequently develops through secondary mutations or pathway bypass mechanisms. In summary: The term "Receptor tyrosine-protein kinase erbB family member" refers collectively to several highly homologous but distinct therapeutic targets central to oncology drug development.

Other names

Epidermal growth factor receptor (EGFR)Human epidermal growth factor receptor 1 (HER1)Erb-b2 receptor tyrosine kinase 2 (HER2, neu)Erb-b3 receptor tyrosine kinase 3 (HER3)Erb-b4 receptor tyrosine kinase 4 (HER4)Type I RTKClass I RTK

Drugs act by one or more of the following mechanisms depending on the target member and drug class: - Inhibition of ligand binding to extracellular domain - Inhibition of intracellular tyrosine kinase activity - Induction of immune-mediated cytotoxicity against cells expressing the target - Delivery of cytotoxic agents specifically to overexpressing cells via antibody-drug conjugates