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Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII).

Publication ,  Journal Article
Chu, CT; Everiss, KD; Wikstrand, CJ; Batra, SK; Kung, HJ; Bigner, DD
Published in: Biochem J
June 15, 1997

The type-III deletion variant of the epidermal growth factor receptor (EGFRvIII) is frequently found in glioblastomas and other malignant human tumours. Although EGFRvIII confers ligand-independent oncogenic transformation of cell lines, the mechanism by which it promotes aberrant cellular proliferation is unknown. Using cell lines expressing comparable numbers of either wild-type receptor (EGFRwt) or EGFRvIII, we compared several parameters of receptor activation: dimerization, tyrosine phosphorylation and activation of intracellular signalling proteins. Like activated EGFRwt, EGFRvIII was phosphorylated and bound constitutively to the Shc adapter protein. Indeed, EGFRvIII-associated Shc had a higher phosphotyrosine content than Shc associated with stimulated EGFRwt. EGFRwt dimerized in response to either EGF or transforming growth factor alpha. Higher cross-linker concentrations and incubation at higher temperatures (37 degrees C) allowed detection of EGFRwt dimers even in the absence of exogenous ligand. In contrast, EGFRvIII failed to dimerize under any conditions studied. Moreover, neither mitogen-activated protein kinase nor phospholipase Cgamma were phosphorylated in EGFRvIII-expressing cells. We conclude that the deletion of 267 amino acids from the 621-amino-acid N-terminal domain of EGFR does not result simply in a constitutively activated receptor, but alters the spectrum of signalling cascades utilized. Furthermore the ligand-independent transforming activity of EGFRvIII is independent of receptor dimerization.

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Published In

Biochem J

DOI

ISSN

0264-6021

Publication Date

June 15, 1997

Volume

324 ( Pt 3)

Issue

Pt 3

Start / End Page

855 / 861

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Signal Transduction
  • Receptors, Cell Surface
  • Humans
  • ErbB Receptors
  • Dimerization
  • Biochemistry & Molecular Biology
  • 3101 Biochemistry and cell biology
  • 11 Medical and Health Sciences
  • 06 Biological Sciences
 

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Chu, C. T., Everiss, K. D., Wikstrand, C. J., Batra, S. K., Kung, H. J., & Bigner, D. D. (1997). Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII). Biochem J, 324 ( Pt 3)(Pt 3), 855–861. https://doi.org/10.1042/bj3240855
Chu, C. T., K. D. Everiss, C. J. Wikstrand, S. K. Batra, H. J. Kung, and D. D. Bigner. “Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII).Biochem J 324 ( Pt 3), no. Pt 3 (June 15, 1997): 855–61. https://doi.org/10.1042/bj3240855.
Chu CT, Everiss KD, Wikstrand CJ, Batra SK, Kung HJ, Bigner DD. Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII). Biochem J. 1997 Jun 15;324 ( Pt 3)(Pt 3):855–61.
Chu, C. T., et al. “Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII).Biochem J, vol. 324 ( Pt 3), no. Pt 3, June 1997, pp. 855–61. Pubmed, doi:10.1042/bj3240855.
Chu CT, Everiss KD, Wikstrand CJ, Batra SK, Kung HJ, Bigner DD. Receptor dimerization is not a factor in the signalling activity of a transforming variant epidermal growth factor receptor (EGFRvIII). Biochem J. 1997 Jun 15;324 ( Pt 3)(Pt 3):855–861.
Journal cover image

Published In

Biochem J

DOI

ISSN

0264-6021

Publication Date

June 15, 1997

Volume

324 ( Pt 3)

Issue

Pt 3

Start / End Page

855 / 861

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Signal Transduction
  • Receptors, Cell Surface
  • Humans
  • ErbB Receptors
  • Dimerization
  • Biochemistry & Molecular Biology
  • 3101 Biochemistry and cell biology
  • 11 Medical and Health Sciences
  • 06 Biological Sciences