HER3

HER3‏‎ (also known as ErbB3) is a member of the ErbB family of receptor tyrosine kinases. These proteins are involved in the regulation of cell growth, survival, and differentiation. HER3‏‎ is unique among the ErbB proteins in that it has a defective kinase domain and therefore relies on heterodimerization with other ErbB proteins for its activity.

Structure[edit | edit source]

HER3‏‎ is a single-pass type I membrane protein. It is composed of an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain is responsible for ligand binding, while the intracellular domain contains the defective kinase domain and several phosphorylation sites.

Function[edit | edit source]

HER3‏‎ is activated by the binding of its ligand, heregulin, to its extracellular domain. This leads to the formation of heterodimers with other ErbB proteins, most commonly HER2‏‎. The heterodimerization leads to the activation of the kinase domain of the partner protein, which in turn phosphorylates the intracellular domain of HER3‏‎. This phosphorylation triggers a cascade of intracellular signaling pathways, including the PI3K/AKT pathway and the RAS/RAF/MEK/ERK pathway, which regulate cell growth and survival.

Clinical significance[edit | edit source]

Abnormal activation of HER3‏‎ has been implicated in the development and progression of several types of cancer, including breast cancer, ovarian cancer, and lung cancer. In particular, overexpression of HER3‏‎ and its partner protein HER2‏‎ is associated with poor prognosis in breast cancer. Therefore, HER3‏‎ is a potential target for cancer therapy, and several monoclonal antibodies and small molecule inhibitors targeting HER3‏‎ are currently in clinical development.