Abstract
The MET protooncogene encodes p190MET, a tyrosine kinase which is the receptor for a molecule known as scatter factor or hepatocyte growth factor (SF/HGF). This molecule has different biological activities, including stimulation of cell motility, promotion of matrix invasion and, in some cells, mitogenesis. We have cloned the full-length MET cDNA and transfected it into NIH 3T3 fibroblasts. Stable transfectants expressed the p190MET receptor together with two previously described truncated forms of 140 and 130 kDa lacking the tyrosine kinase domain. All three forms bound radiolabeled SF/HGF. The factor stimulated tyrosine kinase activity of the transfected p190MET and induced changes in cell shape, migration in Boyden chambers, and invasion of collagen matrices in vitro. The motile and invasive phenotype was transient and strictly dependent on the presence of SF/HGF. The factor did not stimulate either cell growth or thymidine incorporation in transfected cells, while it promoted colony formation in soft agar in the presence of 5% fetal calf serum. These data show that, in the presence of its ligand, the MET receptor expressed in fibroblasts induces cells to pursue a motogenic-invasive rather than a proliferative program.
| Original language | English |
|---|---|
| Pages (from-to) | 649-653 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 90 |
| Issue number | 2 |
| Publication status | Published - Jan 15 1993 |
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Keywords
- Invasion
- Tyrosine kinase receptors
ASJC Scopus subject areas
- General
- Genetics
Cite this
Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene. / Giordano, S.; Zhen, Z.; Medico, E.; Gaudino, G.; Galimi, F.; Comoglio, P. M.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 2, 15.01.1993, p. 649-653.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transfer of motogenic and invasive response to scatter factor/hepatocyte growth factor by transfection of human MET protooncogene
AU - Giordano, S.
AU - Zhen, Z.
AU - Medico, E.
AU - Gaudino, G.
AU - Galimi, F.
AU - Comoglio, P. M.
PY - 1993/1/15
Y1 - 1993/1/15
N2 - The MET protooncogene encodes p190MET, a tyrosine kinase which is the receptor for a molecule known as scatter factor or hepatocyte growth factor (SF/HGF). This molecule has different biological activities, including stimulation of cell motility, promotion of matrix invasion and, in some cells, mitogenesis. We have cloned the full-length MET cDNA and transfected it into NIH 3T3 fibroblasts. Stable transfectants expressed the p190MET receptor together with two previously described truncated forms of 140 and 130 kDa lacking the tyrosine kinase domain. All three forms bound radiolabeled SF/HGF. The factor stimulated tyrosine kinase activity of the transfected p190MET and induced changes in cell shape, migration in Boyden chambers, and invasion of collagen matrices in vitro. The motile and invasive phenotype was transient and strictly dependent on the presence of SF/HGF. The factor did not stimulate either cell growth or thymidine incorporation in transfected cells, while it promoted colony formation in soft agar in the presence of 5% fetal calf serum. These data show that, in the presence of its ligand, the MET receptor expressed in fibroblasts induces cells to pursue a motogenic-invasive rather than a proliferative program.
AB - The MET protooncogene encodes p190MET, a tyrosine kinase which is the receptor for a molecule known as scatter factor or hepatocyte growth factor (SF/HGF). This molecule has different biological activities, including stimulation of cell motility, promotion of matrix invasion and, in some cells, mitogenesis. We have cloned the full-length MET cDNA and transfected it into NIH 3T3 fibroblasts. Stable transfectants expressed the p190MET receptor together with two previously described truncated forms of 140 and 130 kDa lacking the tyrosine kinase domain. All three forms bound radiolabeled SF/HGF. The factor stimulated tyrosine kinase activity of the transfected p190MET and induced changes in cell shape, migration in Boyden chambers, and invasion of collagen matrices in vitro. The motile and invasive phenotype was transient and strictly dependent on the presence of SF/HGF. The factor did not stimulate either cell growth or thymidine incorporation in transfected cells, while it promoted colony formation in soft agar in the presence of 5% fetal calf serum. These data show that, in the presence of its ligand, the MET receptor expressed in fibroblasts induces cells to pursue a motogenic-invasive rather than a proliferative program.
KW - Invasion
KW - Tyrosine kinase receptors
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M3 - Article
C2 - 8380644
AN - SCOPUS:0027458940
VL - 90
SP - 649
EP - 653
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 2
ER -