Human epidermal growth factor receptor family tyrosine kinase (HER family (also known as ErbB family))

The **HER family tyrosine kinases**—also known as the **ErbB receptor family**—comprise four closely related plasma membrane-bound receptor tyrosine kinases: EGFR/HER1/ErbB1, HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4. Each member contains an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular region with a conserved protein tyrosine kinase domain. These receptors mediate signal transduction from extracellular growth factors into cellular responses that regulate cell proliferation and survival. Upon ligand binding or heterodimerization among different members—especially involving HER2 as a preferred partner—their cytoplasmic domains become autophosphorylated on specific tyrosines. This triggers downstream signaling cascades including MAPK and PI3K/Akt pathways that promote cell division while inhibiting apoptosis. Dysregulation of these receptors—most notably overexpression or gene amplification of **HER2**—drives oncogenesis in several cancers such as breast cancer. As such, they are major therapeutic targets for monoclonal antibodies and small-molecule inhibitors designed to block their function at various levels.

Other names

ErbB familyEpidermal growth factor receptor familyHER receptorsERBB1, ERBB2, ERBB3, ERBB4 (individual members)Receptor tyrosine-protein kinase erbB-1/2/3/4

Drugs act via mechanisms such as: - Inhibition of receptor dimerization and activation (e.g., monoclonal antibodies like trastuzumab block extracellular domain interactions) - Inhibition of intracellular tyrosine kinase activity (e.g., small molecule inhibitors like lapatinib bind to the ATP-binding site of the kinase domain)