Recombinant Mouse EGFR Fc Chimera Protein, CF

The EGFR subfamily of receptor tyrosine kinases comprises four members: EGFR (also known as HER-1, ErbB1, or ErbB), ErbB2 (Neu, HER-2), ErbB3 (HER-3), and ErbB4 (HER-4). All family members are type I transmembrane glycoproteins. They contain an extracellular ligand binding domain containing two cysteine-rich domains and a cytoplasmic domain containing a membrane-proximal tyrosine kinase domain followed by multiple tyrosine autophosphorylation sites (1, 2). The mouse EGFR cDNA encodes a 1210 amino acid (aa) precursor with a 24 aa signal peptide, a 623 aa extracellular domain (ECD), a 23 aa transmembrane segment, and a 540 aa cytoplasmic domain (3). Soluble receptors consisting of the extracellular ligand binding domain are generated by alternate splicing in human and mouse (4-6). Within the ECD, mouse EGFR shares 88% and 93% aa sequence identity with human and rat EGFR, respectively. It shares 44%-48% aa sequence identity with the ECD of mouse ErbB2, ErbB3, and ErbB4. EGFR binds a subset of the EGF family ligands, including EGF, amphiregulin, TGF-alpha, betacellulin, epiregulin, HB-EGF, and epigen (1, 2). Ligand binding induces EGFR homodimerization as well as heterodimerization with ErbB2, resulting in kinase activation, heterodimerization tyrosine phosphorylation and cell signaling (7-11). EGFR can also be recruited to form heterodimers with the ligand-activated ErbB3 or ErbB4. EGFR signaling regulates multiple biological functions including cell proliferation, differentiation, motility, and apoptosis (12, 13). EGFR is over-expressed in a wide variety of tumors and is the target of several anti-cancer drugs (14).