The motility signal of scatter factor/hepatocyte growth factor mediated through the receptor tyrosine kinase met requires intracellular action of Ras.
Scatter factor/hepatocyte growth factor (SF/HGF) has various biological effects upon different cells, i.e. induces increased motility and proliferation as well as invasiveness and morphogenesis. The signals given to epithelial cells by SF/HGF are all mediated through the Met receptor tyrosine kinase (Weidner, K. M., Sachs, M., and Birchmeier, W. (1993) J. Cell Biol. 111, 145-154) suggesting that signal diversity is due to the interplay of different downstream pathways. It has also been shown that SF/HGF activates the protooncogene product Ras, i.e. stimulates guanine nucleotide exchange. In order to examine whether Ras is involved in mediating the dissociation and motility signal of SF/HGF to epithelial cells, we have expressed in Madin-Darby canine kidney cells the dominant-negative N17Ras under the control of a modified metallothionein promoter. Induced expression of N17Ras by the addition of Zn2+ clearly prevented dissociation of the cells by SF/HGF. These data indicate that the Ras pathway is indeed essential to mediate the motility signal of SF/HGF-Met to the cell-cell adhesion system and the cytoskeleton of epithelial cells.
Hartmann
G
G
Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Federal Republic of Germany.
Weidner
K M
KM
Schwarz
H
H
Birchmeier
W
W
D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D004285:Dogs; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D015689:Oncogene Protein p21(ras)