The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells.
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.
Institute of Cell Biology, Tumor Research, University of Essen Medical School, Germany.
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KM
Weidner
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M
Sachs
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Birchmeier
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D003001:Cloning, Molecular; D004247:DNA; D004285:Dogs; D004847:Epithelial Cells; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D017228:Hepatocyte Growth Factor; D004247:DNA; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met