Receptor tyrosine-protein kinase erbB-3 (HER3)

Receptor tyrosine-protein kinase erbB‑3 (HER3/ERBB3) is a member of the epidermal growth factor receptor family of type I transmembrane proteins. It consists of an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular region with a pseudokinase domain that has very weak intrinsic catalytic activity. Unlike other ERBB family members, ERBB3 relies primarily on heterodimerization—especially with ERBB2/HER2—to activate downstream signaling pathways such as PI3K/Akt following ligand binding by neuregulins. This unique mechanism makes it central to both normal developmental processes and oncogenic signaling. HER3 is highly expressed in many cancers and plays a key role in resistance mechanisms against EGFR/HER2-targeted therapies. As such, it is considered an important therapeutic target; several investigational monoclonal antibodies have been developed that inhibit its function by blocking ligand binding or dimerization. However, direct inhibition remains challenging due to its limited enzymatic activity compared with other kinases.

Other names

HER3ERBB3ErbB-3Proto-oncogene-like protein c-ErbB-3Tyrosine kinase-type cell surface receptor HER3

Monoclonal antibodies block ligand binding or dimerization with other ErbB receptors. Locking the extracellular domain in an inactive conformation. Preventing phosphorylation and downstream signaling. Inducing antibody-dependent cellular cytotoxicity.