Mutation of juxtamembrane tyrosine residue 1001 suppresses loss-of- function mutations of the met receptor in epithelial cells

K. M. Weidner, M. Sachs, D. Riethmacher, W. Birchmeier

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Signals transduced by the met tyrosine kinase, which is the receptor for scatter factor/hepatocyte growth factor, are of major importance for the regulation of epithelial cell motility, morphogenesis, and proliferation. We report here that different sets of tyrosine residues in the cytoplasmic domain of the met receptor affect signal transduction in epithelial cells in a positive or negative fashion: mutation of the C-terminal tyrosine residues 13-16 (Y1311, Y1347, Y1354, and Y1363) reduced or abolished ligand-induced cell motility and branching morphogenesis. In contrast, mutation of the juxtamembrane tyrosine residue 2 (Y!001) produced constitutively mobile, fibroblastoid cells. Furthermore, the gain-of-function mutation of tyrosine residue 2 suppressed the loss-of-function mutations of tyrosine residue 15 or 16. The opposite roles of the juxtamembrane and C-terminal tyrosine residues may explain the suggested dual function of the met receptor in both epithelial-mesenchymal interactions and tumor progression.

Original languageEnglish
Pages (from-to)2597-2601
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number7
DOIs
Publication statusPublished - 1995

Keywords

  • branching morphogenesis
  • cell motility
  • epithelial-mesenchymal interactions
  • hepatocyte growth factor
  • scatter factor
  • signal transduction

ASJC Scopus subject areas

  • General

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