Deletion-mutant epidermal growth factor receptor in human gliomas: effects of type II mutation on receptor function

Biochem Biophys Res Commun. 1991 Aug 15;178(3):1413-20. doi: 10.1016/0006-291x(91)91051-d.

Abstract

Malignant human glioma D-298 MG amplifies a rearranged epidermal growth factor receptor (EGFR) gene (c-erbB proto-oncogene), resulting in an in-frame deletion of 83 amino acids in domain IV of the extracellular domain of the EGFR. EGF and transforming growth factor-a (TGF-a) bound to the mutant EGFR with high affinity and enhanced the intrinsic mutant EGFR kinase activity. The mutant EGFR was capable of transducing EGF-stimulated glioma cell proliferation and invasiveness in an in vitro three-dimensional spheroid model. The deletion-mutant EGFR in D-298 MG is capable of being activated by growth factor; this suggests that overexpression of this mutant EGFR protein rather than structural alteration may be the more significant biologic event.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Chromosome Deletion*
  • Epidermal Growth Factor / metabolism
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Gene Amplification*
  • Gene Rearrangement*
  • Glioma / genetics
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogenes*
  • Receptor, ErbB-2
  • Transforming Growth Factor alpha / metabolism
  • Transforming Growth Factor alpha / pharmacology*

Substances

  • Proto-Oncogene Proteins
  • Transforming Growth Factor alpha
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2

Associated data

  • GENBANK/S50206
  • GENBANK/S50208
  • GENBANK/S50210
  • GENBANK/S50212
  • GENBANK/S50216
  • GENBANK/S50220
  • GENBANK/S50222
  • GENBANK/S50224
  • GENBANK/S51292
  • GENBANK/S51343