A single amino acid substitution is sufficient to modify the mitogenic properties of the epidermal growth factor receptor to resemble that of gp185erbB-2

Pier Paolo Di Fiore, Kristian Helin, Matthias H. Kraus, Jacalyn H. Pierce, Jennifer Artrip, Oreste Segatto, Donald P. Bottaro

Research output: Contribution to journalArticlepeer-review

Abstract

The epidermal growth factor (EGF) receptor (EGFR) and the erb B-2 gene product, gp185erbB-2, exhibit distinct abilities to stimulate mitogenesis in different target cells. By using chimeric molecules between these two receptors, we have previously shown that their intracellular juxta-membrane regions are responsible for this specificity. Here we describe a genetically engineered EGFR mutant containing a threonine for arginine substitution at position 662 in the EGFR juxtamembrane domain, corresponding to threonine 694 in gp185erbB-2. This mutant, designated EGFRThr662, displayed affinity for EGF binding and catalytic properties that were indistinguishable from those of the wild type EGFR. However, EGFRThr662 behaved much as gp185erbB-2 in a number of bioassays which readily distinguish between the mitogenic effects of EGFR and gp185erbB-2. Moreover, significant differences were detected in the pattern of intracellular proteins phosphorylated on tyrosine in vivo by EGFR and EGFRThr662 in response to EGF. Thus, small differences in the primary sequence of two closely related receptors have dramatic effects on their ability to couple with mitogenic pathways.

Original languageEnglish
Pages (from-to)3927-3933
Number of pages7
JournalEMBO Journal
Volume11
Issue number11
Publication statusPublished - Nov 1992

Keywords

  • EGFR
  • erbB-2
  • Signal transduction
  • Substrates
  • Tyrosine kinases

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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