The EGF receptor: structure, regulation and potential role in malignancy.
Retroviral onc genes are derived from cellular proto-oncogenes that may function in normal cellular growth control. The epidermal growth factor (EGF) receptor is the proto-oncogene of erbB; both possess intrinsic protein tyrosine kinase activity, a property shared by several retroviral onc genes. The EGF receptor is a transmembrane glycoprotein with an external EGF binding domain and a cytoplasmic region that is homologous with other tyrosine kinases. erbB lacks the EGF binding and carboxyl terminal regions, which are thought to be important in regulation. The EGF receptor is regulated by several mechanisms: stimulation by ligand binding and self-phosphorylation, inhibition by heterologous phosphorylation and downregulation by ligand. EGF binding stimulates several early events, including phosphatidylinositol (PI) turnover in A431 cells. A PI kinase activity copurifies with the EGF receptor and some other tyrosine kinases, but this is a contaminant as it can be separated from the EGF receptor. Although the role of proto-onc genes in human malignancy is incompletely defined, increased numbers of EGF receptors are present in several types of human tumours. Overexpression of EGF receptors, as occurs in human epidermoid carcinoma A431 cells, can augment cell growth because of increased formation of active ligand:receptor complexes. Gene amplification is the mechanism underlying overexpression of EGF receptors in A431 cells and in some glioblastoma multiforme tumours.
Thompson
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DM
Department of Medicine, University of California, San Diego, School of Medicine, La Jolla 92093.
Gill
G N
GN
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002471:Cell Transformation, Neoplastic; D066246:ErbB Receptors / Q000032:analysis / Q000502:physiology; D006801:Humans; D009857:Oncogenes; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D066246:ErbB Receptors