Analysis of Functional Domains in the Epidermal Growth Factor Receptor Using Site-Directed Mutagenesis

  • Gordon N. Gill
  • Michael G. Rosenfeld
  • William S. Chen
  • Paul J. Bertics
  • Cheri S. Lazar
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 234)


Protein tyrosine kinase activity is a central feature of one class of retroviral onc genes and of several growth factor receptors including those for epidermal growth factor receptor (EGF) (Ushiro and Cohen, 1980; Hunter and Cooper, 1985), platelet-derived growth factor (PDGF) (Yarden et al., 1986), insulin and insulin-like growth factors (IGF) (Ebina et al., 1985; Ullrich et al., 1985), colony-stimulating factor 1 (CSF1) (Sherr et al., 1985), and other ligands (neu) (Bargmann et al., 1986a; Yamamoto et al., 1986). The EGF receptor is the proto-oncogene for the retroviral oncogene erb B (Yamamoto et al., 1983; Downward et al., 1984a; Lin et al., 1984; Ullrich et al., 1984; Xu et al., 1984); the CSF1 receptor for v-fms (Sherr et al., 1985; Coussens et al., 1986); and the neu receptor for the transforming gene neu (Bargmann et al., 1986b). The sis oncogene of the simian sarcoma virus is homologous to the B chain of PDGF and presumably exerts its transforming effects through interaction with the normal PDGF receptor (Doolittle et al., 1983; Waterfield et al., 1983; Huang et al., 1984). Constitutive expression of TGF-α and of EGF, both of which bind to the EGF receptor, also results in cell transformation, presumably via activation of normal EGF receptors (Rosenthal et al., 1986; Stern et al., 1987). Constitutive activation of ligands may be analogous to gene amplification and quantitative over-expression of receptor protein as occurs in some human tumors (Thompson and Gill, 1985) because the initial ligand receptor interaction in a bimolecular event dependent on the concentration of both ligand and receptor (Gill et al., 1985).


Epidermal Growth Factor Receptor A431 Cell Human Epidermal Growth Factor Receptor Mutant Epidermal Growth Factor Receptor Carboxyl Terminus 
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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Gordon N. Gill
    • 1
  • Michael G. Rosenfeld
    • 1
  • William S. Chen
    • 1
  • Paul J. Bertics
    • 1
  • Cheri S. Lazar
    • 1
  1. 1.Division of Endocrinology and Metabolism and Eukaryotic Regulatory Biology Program, Department of MedicineUniversity of California, San Diego, School of MedicineLa JollaUSA

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