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

102 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
Externally publishedYes

Fingerprint

Tyrosine
Epithelial Cells
Mutation
Morphogenesis
Cell Movement
Proto-Oncogene Proteins c-met
Hepatocyte Growth Factor
Protein-Tyrosine Kinases
Signal Transduction
Cell Proliferation
Ligands
Neoplasms
2-tyrosine

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{c583d3de9a9047a784568d791be737a2,
title = "Mutation of juxtamembrane tyrosine residue 1001 suppresses loss-of- function mutations of the met receptor in epithelial cells",
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.",
keywords = "branching morphogenesis, cell motility, epithelial-mesenchymal interactions, hepatocyte growth factor, scatter factor, signal transduction",
author = "Weidner, {K. M.} and M. Sachs and D. Riethmacher and W. Birchmeier",
year = "1995",
doi = "10.1073/pnas.92.7.2597",
language = "English",
volume = "92",
pages = "2597--2601",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "7",

}

TY - JOUR

T1 - Mutation of juxtamembrane tyrosine residue 1001 suppresses loss-of- function mutations of the met receptor in epithelial cells

AU - Weidner, K. M.

AU - Sachs, M.

AU - Riethmacher, D.

AU - Birchmeier, W.

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

KW - branching morphogenesis

KW - cell motility

KW - epithelial-mesenchymal interactions

KW - hepatocyte growth factor

KW - scatter factor

KW - signal transduction

UR - http://www.scopus.com/inward/record.url?scp=0028940362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028940362&partnerID=8YFLogxK

U2 - 10.1073/pnas.92.7.2597

DO - 10.1073/pnas.92.7.2597

M3 - Article

VL - 92

SP - 2597

EP - 2601

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 7

ER -