The epidermal growth factor receptor （EGF R） subfamily of receptor tyrosine kinases comprises four members: EGF R （also known as HER1， ErbB1 or ErbB）， ErbB2 （Neu， HER-2）， ErbB3 （HER-3）， and ErbB4 （HER-4）. All family members are type I transmembrane glycoprotein that has an extracellular domain which contains two cysteine-rich domains separated by a spacer region that is involved in ligand-binding， and a cytoplasmic domain which has a membrane-proximal tyrosine kinase domain and a C-terminal tail with multiple tyrosine autophosphorylation sites. The human EGF R gene encodes a 1210 amino acid （aa） residue precursor with a 24 aa putative signal peptide， a 621 aa extracellular domain， a 23 aa transmembrane domain， and a 542 aa cytoplasmic domain. EGF R has been shown to bind a subset of the EGF family ligands， including EGF， amphiregulin， TGF-? ， betacellulin， epiregulin， heparin-binding EGF and neuregulin-2 in the absence of a co-receptor. Ligand binding induces EGF R homodimerization as well as heterdimerization with ErbB2， resulting in kinase activation， tyrosine phosphorylation and cell signaling. EGF R can also be recruited to form heterodimers with the ligand-activated ErbB3 or ErbB4. EGF R signaling has been shown to regulate multiple biological functions including cell proliferation， differentiation， motility and apoptosis. In addition， EGF R signaling has also been shown to play a role in carcinogenesis.
