MUTATION OF JUXTAMEMBRANE TYROSINE RESIDUE-1001 SUPPRESSES LOSS-OF-FUNCTION MUTATIONS OF THE MET RECEPTOR IN EPITHELIAL-CELLS

被引:104
作者
WEIDNER, KM
SACHS, M
RIETHMACHER, D
BIRCHMEIER, W
机构
[1] Max-Delbruck-Ctr. for Molecular Med., 13125 Berlin
关键词
SCATTER FACTOR HEPATOCYTE GROWTH FACTOR; CELL MOTILITY; BRANCHING MORPHOGENESIS; SIGNAL TRANSDUCTION; EPITHELIAL-MESENCHYMAL INTERACTIONS;
D O I
10.1073/pnas.92.7.2597
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2597 / 2601
页数:5
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