PubMed Journals: Proc Natl Acad Sci U S A
Source: PMID: 7708691
⇦ ⇨ Proc Natl Acad Sci U S A. 1995 Mar
Mutation of juxtamembrane tyrosine residue
1001 suppresses loss-of-function mutations
of the met receptor in epithelial cells.
Weidner KM(1), Sachs M, Riethmacher D, Birchmeier
(1) Max-Delbrück-Center for Molecular Medicine,
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 (Y1001) 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.
PMCID: PMC42265 PMID: 7708691 [Indexed