A variant epidermal growth factor receptor exhibits altered type α transforming growth factor binding and transmembrane signaling

Tetsuya Moriai, Michael S. Kobrin, Christopher Hope, Lynn Speck, Murray Korc

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Epidermal growth factor (EGF) and type α transforming growth factor (TGF- α) bind to a specific region in subdomain III of the extracellular portion of the EGF receptor (EGFR). Binding leads to receptor dimerization, auto- and transphosphorylation on intracellular tyrosine residues, and activation of signal transduction pathways. We compared the binding and biological actions of EGF and TGF-α in Chinese hamster ovary (CHO) cells expressing either wild-type human EGFR (HER497R) or a variant EGFR that has an arginine-to- lysine substitution in the extracellular domain at codon 497 (HER497K) within subdomain IV of EGFR. Both receptors exhibited two orders of binding sites with radioiodinated EGF (125I-EGF). Similar results were obtained with 125I-TGF-α in cells expressing HER497R. In contrast, only one order of low-affinity binding sites was seen with 125I-TGF-α in the case of HER497K. Although EGF and TGF-α enhanced tyrosine phosphorylation of both receptors, CHO cells expressing HER497K exhibited an attenuated growth response to EGF and TGF-α and a reduced induction of the protooncogenes FOS, JUN, and MYC. Moreover, high concentrations of TGF-α (5 nM) inhibited growth in these cells but not in cells expressing HER497R. These findings indicate that a region in subdomain IV of EGFR regulates signal transduction across the cell membrane and selectively modulates the binding characteristics of TGF-α.

Original languageEnglish (US)
Pages (from-to)10217-10221
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number21
DOIs
StatePublished - Oct 11 1994
Externally publishedYes

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Transforming Growth Factors
Epidermal Growth Factor Receptor
Epidermal Growth Factor
Cricetulus
Tyrosine
Ovary
Signal Transduction
Binding Sites
Dimerization
Growth
Codon
Lysine
Arginine
Phosphorylation
Cell Membrane

Keywords

  • protooncogenes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A variant epidermal growth factor receptor exhibits altered type α transforming growth factor binding and transmembrane signaling. / Moriai, Tetsuya; Kobrin, Michael S.; Hope, Christopher; Speck, Lynn; Korc, Murray.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 21, 11.10.1994, p. 10217-10221.

Research output: Contribution to journalArticle

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