Receptor tyrosine-protein kinase erbB-2 (HER2)

Receptor tyrosine-protein kinase erbB-2 (HER2), encoded by the ERBB2 gene, is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. Unlike other ErbB receptors, HER2 does not have a known direct ligand and is constitutively in an open conformation that favors dimerization with other ErbB family members or itself when overexpressed. Activation through heterodimerization with other ErbB receptors, especially HER3, or homodimerization when overexpressed, leads to autophosphorylation of tyrosine residues and activation of downstream signaling pathways, including MAPK, PI3K/Akt, PLCγ, PKC, and STAT pathways. These pathways regulate cellular processes such as proliferation, survival, differentiation, angiogenesis, invasion, and metastasis. Overexpression or amplification of HER2 is found in approximately 20% of breast cancers and is associated with aggressive tumor behavior and poor prognosis, but it also makes tumors amenable to targeted therapies.

Other names

ERBB2p185erbB2Proto-oncogene c-ErbB-2Metastatic lymph node gene 19 proteinProto-oncogene NeuNeu

Inhibition of HER2 kinase activity or blocking HER2 dimerization, leading to decreased downstream signaling.