| Background |
The epidermal growth factor receptor (EGFR), also known as ErbB-1 or HER1, is the cell-surface receptor for members of the epidermal growth factor (EGF) family. Epidermal growth factor (EGF) is a growth factor that stimulates cell growth, proliferation, and differentiation and the founding member of the EGF-family. The other members of this protein family include: Heparin-binding EGF-like growth factor (HB-EGF), transforming growth factor-α (TGF-α), Amphiregulin (AR), Epiregulin (EPR), Epigen, Betacellulin (BTC), neuregulin-1 (NRG1), neuregulin-2 (NRG2), neuregulin-3 (NRG3), and neuregulin-4 (NRG4). EGFR is a member of the ErbB family, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). The full-length 1210 amino acid (aa) human EGFR precursor protein consists of a 24 aa signal peptide, a 621 aa extracellular domain (ECD), a 23 aa transmembrane segment, and a 542 aa cytoplasmic domain. Within the ECD, human EGFR shares 88% aa sequence identity with mouse and rat EGFR, and shares 43%-44% aa sequence identity with human ErbB2, ErbB3, and ErbB4. EGFR binds several proteins of the EGF family, including EGF, amphiregulin, TGFα, betacellulin, epiregulin, HBEGF, and epigen. Ligand binding induces EGFR homodimerization as well as heterodimerization with ErbB2 and initiates a series of biological processes involved in cell proliferation, differentiation, motility, and apoptosis. EGFR overexpression or overactivity have been associated with a number of cancers, including lung cancer, anal cancers and glioblastoma. |
