Erbb1/EGFR (EGFR) Active Protein

EGFR: 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.

Protein type: Kinase, protein; Tumor suppressor; Protein kinase, TK; Membrane protein, integral; EC 2.7.10.1; Protein kinase, tyrosine (receptor); TK group; EGFR family

Cellular Component: Golgi apparatus; focal adhesion; cell surface; endoplasmic reticulum; basolateral plasma membrane; integral to membrane; lipid raft; membrane; perinuclear region of cytoplasm; endocytic vesicle; apical plasma membrane; cytoplasm; plasma membrane; endosome membrane; intracellular; nucleus; endosome; receptor complex

Molecular Function: identical protein binding; epidermal growth factor receptor activity; epidermal growth factor binding; nitric-oxide synthase regulator activity; nucleotide binding; transmembrane receptor protein tyrosine kinase activity; receptor signaling protein tyrosine kinase activity; protein kinase binding; protein phosphatase binding; protein kinase activity; transferase activity; actin filament binding; integrin binding; protein binding; signal transducer activity; enzyme binding; transmembrane receptor activity; protein heterodimerization activity; protein-tyrosine kinase activity; ubiquitin protein ligase binding; transferase activity, transferring phosphorus-containing groups; chromatin binding; kinase activity; glycoprotein binding; ATP binding; receptor binding

Biological Process: positive regulation of nitric oxide biosynthetic process; activation of MAPKK activity; multicellular organismal development; positive regulation of vasodilation; G1/S-specific positive regulation of cyclin-dependent protein kinase activity; protein amino acid phosphorylation; positive regulation of MAP kinase activity; positive regulation of fibroblast proliferation; cell-cell adhesion; cell surface receptor linked signal transduction; ovulation cycle; hair follicle development; positive regulation of superoxide release; negative regulation of mitotic cell cycle; positive regulation of DNA repair; digestive tract morphogenesis; positive regulation of transcription from RNA polymerase II promoter; regulation of nitric-oxide synthase activity; response to calcium ion; negative regulation of protein catabolic process; transmembrane receptor protein tyrosine kinase signaling pathway; positive regulation of epithelial cell proliferation; negative regulation of apoptosis; epidermis development; embryonic placenta development; peptidyl-tyrosine phosphorylation; translation; protein amino acid autophosphorylation; positive regulation of smooth muscle cell proliferation; cell morphogenesis; signal transduction; positive regulation of synaptic transmission, glutamatergic; learning and/or memory; positive regulation of cell proliferation; salivary gland morphogenesis; regulation of peptidyl-tyrosine phosphorylation; epidermal growth factor receptor signaling pathway; regulation of cell proliferation; cell proliferation; positive regulation of protein kinase B signaling cascade; cerebral cortex cell migration; positive regulation of vasoconstriction; positive regulation of protein amino acid phosphorylation; astrocyte activation; phosphorylation; positive regulation of phosphorylation; neurite morphogenesis; positive regulation of DNA replication; positive regulation of inflammatory response; positive regulation of cell migration