a receptor tyrosine kinase. This is a receptor for epidermal growth factor (EGF) and related growth factors including TGF-alpha, amphiregulin, betacellulin, heparin-binding EGF-like growth factor, GP30, and vaccinia virus growth factor. EGFR is involved in the control of cell growth and differentiation. It is a single-pass transmembrane tyrosine kinase. Ligand binding to this receptor results in receptor dimerization, autophosphorylation (in trans), activation of various downstream signaling molecules and lysosomal degradation. It can be phosphorylated and activated by Src. Activated EGFR binds the SH2 domain of phospholipase C-gamma (PLC-gamma), activating PLC-gamma-mediated downstream signaling. Phosphorylated EGFR binds Cbl, leading to its ubiquitination and degradation. Grb2 and SHC bind to phospho-EGFR and are involved in the activation of MAP kinase signaling pathways. Phosphorylation on Ser and Thr residues is thought to represent a mechanism for attenuation of EGFR kinase activity. EGFR is overexpressed in breast, head and neck cancers, correlating with poor survival. Activating somatic mutations are seen in lung cancer, corresponding to the minority of patients with strong responses to the EGFR inhibitor Iressa (gefitinib). Mutations and amplifications are also seen in glioblastoma, and upregulation is seen in colon cancer and neoplasms. In xenografts, inhibitors synergize with cytotoxic drugs in the inhibition of many tumor types. Inhibitors include: Iressa/ZD1839, Erbitux, Tarceva, and lapatinib. Four alternatively spliced isoforms have been described. Note: This description may include information from UniProtKB.
Protein type: EC 188.8.131.52; EGFR family; Kinase, protein; Membrane protein, integral; Protein kinase, TK; Protein kinase, tyrosine (receptor); TK group; Tumor suppressor
Molecular Function: actin filament binding; chromatin binding; enzyme binding; epidermal growth factor receptor activity; identical protein binding; nitric-oxide synthase regulator activity; phosphatidylinositol-4,5-bisphosphate 3-kinase activity; protein binding; protein heterodimerization activity; protein phosphatase binding; protein-tyrosine kinase activity; Ras guanyl-nucleotide exchange factor activity; transmembrane receptor activity; transmembrane receptor protein tyrosine kinase activity; ubiquitin protein ligase binding
Biological Process: calcium-dependent phospholipase A2 activation; cell proliferation; cell surface receptor linked signal transduction; cell-cell adhesion; epidermal growth factor receptor signaling pathway; G1/S-specific positive regulation of cyclin-dependent protein kinase activity; learning and/or memory; MAPKKK cascade; negative regulation of apoptosis; negative regulation of epidermal growth factor receptor signaling pathway; negative regulation of protein catabolic process; phosphoinositide-mediated signaling; phospholipase C activation; positive regulation of cell growth; positive regulation of cell migration; positive regulation of cell proliferation; positive regulation of DNA repair; positive regulation of DNA replication; positive regulation of epithelial cell proliferation; positive regulation of MAP kinase activity; positive regulation of nitric oxide biosynthetic process; positive regulation of phosphorylation; positive regulation of protein amino acid phosphorylation; positive regulation of protein kinase B signaling cascade; positive regulation of transcription from RNA polymerase II promoter; protein amino acid autophosphorylation; protein insertion into membrane; regulation of nitric-oxide synthase activity; regulation of peptidyl-tyrosine phosphorylation; regulation of phosphoinositide 3-kinase cascade; signal transduction