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The Met receptor tyrosine kinase transduces motility, proliferation, andmorphogenic signals of scatter factor/ hepatocyte growth factor in epithelial cells

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Item Type:Article
Title:The Met receptor tyrosine kinase transduces motility, proliferation, andmorphogenic signals of scatter factor/ hepatocyte growth factor in epithelial cells
Creators Name:Weidner, K.M. and Sachs, M. and Birchmeier, W.
Abstract:Depending on the target cells and culture conditions, scatter factor/hepatocyte growth factor (SF/HGF) mediates several distinct activities, i.e., cell motility, proliferation, invasiveness, tubular morphogenesis, angiogenesis, or cytotoxicity. A small isoform of SF/HGF encoded by a natural splice variant, which consists of the NH2-terminal hairpin structure and the first two kringle domains but not the protease homology region, induces cell motility but not mitogenesis. Two types of SF/HGF receptors have recently been discovered in epithelial cells, the high affinity c-Met receptor tyrosine kinase, and low affinity/high capacity binding sites, which are probably located on heparan sulfate proteoglycans. In the present study, we have addressed the question whether the various biological activities of SF/HGF are transduced into cells by a single type of receptor. We have here examined MDCK epithelial cells transfected with a hybrid cDNA encoding the ligand binding domain of the nerve growth factor (NGF) receptor and the membrane-spanning and tyrosine kinase domains of the Met receptor. We demonstrate that all biological effects of SF/HGF upon epithelial cells such as the induction of cell motility, proliferation, invasiveness, and tubular morphogenesis can now be triggered by the addition of NGF. Thus, it is likely that all known biological signals of SF/HGF are transduced through the receptor tyrosine kinase encoded by the c-Met protooncogene.
Keywords:Amino Acid Sequence, Base Sequence, Northern Blotting, Cell Division, Cell Line, Cell Movement, Molecular Cloning, DNA, Epithelial Cells, Hepatocyte Growth Factor, Molecular Sequence Data, Nerve Growth Factors, Phosphorylation, Precipitin Tests, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-met, Cell Surface Receptors, Nerve Growth Factor Receptors, Signal Transduction, Transfection, Animals, Dogs
Source:Journal of Cell Biology
ISSN:0021-9525
Publisher:Rockefeller University Press (U.S.A.)
Volume:121
Number:1
Page Range:145-154
Date:April 1993
Additional Information:Copyright (c) 1993 by The Rockefeller University Press
Official Publication:http://www.jcb.org/cgi/content/abstract/121/1/145
PubMed:View item in PubMed

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