Structural basis for epidermal growth factor receptor function

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Abstract

The receptor for epidermal growth factor (EGF) has been the subject of intense study primarily as a consequence of the pioneering studies of Cohen on growth factors and also because of its homology to the transforming protein encoded by the avian oncogene v-erbB, which is a truncated receptor, and its consequent role in cancer. Although similar structural mutation of the EGF receptor has not yet been found in human tumours, aberrant overexpression of both EGF receptors and c-erbB2, a closely related putative receptor [1], have been found to occur in squamous cell carcinomas and glial tumours, and mammary carcinomas respectively [2–4]. In addition to EGF, the related polypeptides transforming growth factor α (TGFα) and vaccinia virus growth factor [5] are also ligands for the EGF receptor. Expression of TGFα occurs during embryonal development and in specific adult tissues; it may also play a role in cellular transformation (reviewed in Ref. 6). These important properties, as well as the potential roles of both TGFα and EGF in wound repair, have emphasized the need to understand EGF receptor structure, function and regulation. This review discusses the structural properties of the EGF receptor and how these can be related to receptor function and regulation.

References (50)

  • D Cassel et al.

    Proteolytic cleavage of epidermal growth factor receptor

    J Biol Chem.

    (1982)
  • R Seger et al.

    The epidermal growth factor receptor as a substrate for a kinase-splitting membranal proteinase

    J Biol Chem.

    (1988)
  • PJ Bertics et al.

    Self-phosphorylation enhances the protein-tyrosine kinase activity of the epidermal growth factor receptor

    J Biol Chem.

    (1985)
  • S Cohen et al.

    A native 170,000 epidermal growth factor receptor-kinase complex from shed plasma membrane vesicles

    J Biol Chem.

    (1982)
  • BD Morrison et al.

    Insulin stimulation of the insulin receptor kinase can occur in the complete absence of β-subunit autophosphorylation

    J Biol Chem.

    (1987)
  • RJ Davis et al.

    Stimulation of epidermal growth factor receptor threonine 654 phosphorylation by platelet-derived growth factor in protein kinase C-deficient human fibroblasts

    J Biol Chem.

    (1987)
  • RJ Davis

    Independent mechanisms account for the regulation by protein kinase C of the epidermal growth factor receptor affinity and tyrosine-protein kinase activity

    J Biol Chem.

    (1988)
  • M Faucher et al.

    Regulation of the epidermal growth factor receptor phosphorylation state by sphingosine in A431 human epidermal carcinoma cells

    J Biol Chem.

    (1988)
  • L Coussens et al.

    Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene

    Science

    (1985)
  • TA Libermann et al.

    Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin

    Nature

    (1985)
  • WJ Gullick et al.

    Expression of epidermal growth factor receptors on human cervical, ovarian and vulval carcinomas

    Cancer Res

    (1986)
  • DJ Slamon et al.

    Human breast cancer: correlation of relapse and survival with amplification of the HER-2neu oncogene

    Science

    (1987)
  • J Downward et al.

    Close similarity of epidermal growth factor receptor and v-erbB oncogene protein sequences

    Nature

    (1984)
  • A Ullrich et al.

    Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells

    Nature

    (1984)
  • N Shimizu et al.

    Genetics of cell surface receptors for bioactive polypeptides: binding of epidermal growth factor is associated with the presence of human chromosome 7 in human-mouse cell hybrids

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