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5 results on '"C Ronsin"'

1. Macrophage-stimulating protein activates Ras by both activation and translocation of SOS nucleotide exchange factor.

Author

Li BQ, Wang MH, Kung HF, Ronsin C, Breathnach R, Leonard EJ, and Kamata T

Subjects
Animals, Antibodies, Cell Line, Cell Membrane metabolism, Cytosol metabolism, Dogs, Enzyme Activation, ErbB Receptors metabolism, GRB2 Adaptor Protein, Guanine Nucleotide Exchange Factors, Guanosine Diphosphate metabolism, Guanosine Triphosphate metabolism, Humans, Kidney, Kinetics, Macrophages, Mice, Phosphates metabolism, Phosphorylation, Protein Precursors pharmacology, Proteins analysis, Recombinant Proteins metabolism, Transfection, ras Guanine Nucleotide Exchange Factors, Adaptor Proteins, Signal Transducing, Growth Substances pharmacology, Hepatocyte Growth Factor, Proteins metabolism, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases metabolism, Receptors, Cell Surface metabolism, ras Proteins metabolism
Abstract

Macrophage-stimulating protein (MSP) is a chemotactic factor that activates the receptor tyrosine kinase RON. The involvement of Ras in MSP-induced signal transduction was investigated. Here we demonstrate that, in RON-transfected MDCK cells, an active GTP-bound form of Ras was rapidly accumulated by MSP treatment and the Ras-guanine nucleotide exchange activity in SOS immunoprecipitates was concomitantly increased. GAP activity was not changed under the same conditions used. Furthermore, the SH2 domain of adaptor protein GRB2, but not Shc, associated with the activated RON-beta chain, and GRB2-SOS complexes translocated from the cytosol to the membrane upon MSP treatment. These results strongly suggest that MSP activates Ras through RON, and that MSP-induced activation of Ras might be controlled by both the enhancement of catalytic exchange activity of SOS and its translocation to the membrane where its target Ras is localized.

Published
1995
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2. Identification of the ron gene product as the receptor for the human macrophage stimulating protein.

Author

Wang MH, Ronsin C, Gesnel MC, Coupey L, Skeel A, Leonard EJ, and Breathnach R

Subjects
Animals, Binding Sites, Binding, Competitive, Cell Line, Cell Movement drug effects, Cross-Linking Reagents, Dogs, Growth Substances pharmacology, Hepatocyte Growth Factor metabolism, Humans, Phosphorylation, Plasminogen metabolism, Receptor Protein-Tyrosine Kinases genetics, Receptors, Cell Surface genetics, Transfection, Growth Substances metabolism, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases metabolism, Receptors, Cell Surface metabolism
Abstract

Macrophage-stimulating protein (MSP) is a member of the hepatocyte growth factor-scatter factor (HGF-SF) family. Labeled MSP bound to Madin-Darby canine kidney (MDCK) cells transfected with complementary DNA encoding Ron, a cell membrane protein tyrosine kinase. Cross-linking of 125I-labeled MSP to transfected cells (MDCK-RE7 cells) and immunoprecipitation by antibodies to Ron revealed a 220-kilodalton complex, a size consistent with that of MSP (80 kilodaltons) cross-linked to the beta chain of Ron (150 kilodaltons). The binding of 125I-labeled MSP to MDCK-RE7 cells was inhibited by unlabeled MSP, but not by HGF-SF. MSP caused phosphorylation of the beta chain of Ron and induced migration of MDCK-RE7 cells. These results establish the ron gene product as a specific cell-surface receptor for MSP.

Published
1994
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3. A novel putative receptor protein tyrosine kinase of the met family.

Author

Ronsin C, Muscatelli F, Mattei MG, and Breathnach R

Subjects
Amino Acid Sequence, Base Sequence, Cell Line, Chromosome Mapping, Chromosomes, Human, Pair 3, DNA chemistry, DNA genetics, DNA isolation & purification, Gene Expression, Humans, Molecular Sequence Data, Protein-Tyrosine Kinases chemistry, Proto-Oncogene Mas, Proto-Oncogene Proteins chemistry, Proto-Oncogene Proteins c-met, Receptors, Cell Surface chemistry, Protein-Tyrosine Kinases genetics, Proto-Oncogene Proteins genetics, Receptor Protein-Tyrosine Kinases, Receptors, Cell Surface genetics
Abstract

By successive screenings of cDNA libraries prepared from human tumours and from human foreskin keratinocytes, we have isolated overlapping cDNAs coding for a novel protein which we call Ron, with sequence characteristics of a receptor protein tyrosine kinase. Ron is a 1400 amino acid protein structurally similar to the 1408 amino acid product of the C-MET proto-oncogene, the receptor for hepatocyte growth factor and scatter factor. The two proteins have 63% overall sequence identity in their intracellular regions. We have localised the RON gene to human chromosome region 3p21, a region frequently deleted in small cell carcinoma of the lung and in renal cell carcinoma, and which is believed to harbour unidentified tumour suppressor genes. Interestingly, normal lung tissue contains transcripts of the RON gene.

Published
1993

4. Macrophage-Stimulating Protein Activates Ras by both Activation and Translocation of SOS Nucleotide Exchange Factor

Author

H.F. Kung, Richard Breathnach, M.H. Wang, Baoqun Li, C. Ronsin, T. Kamata, and Edward J. Leonard

Subjects
Biophysics, Receptors, Cell Surface, Kidney, Transfection, SH2 domain, Guanosine Diphosphate, Biochemistry, Antibodies, Receptor tyrosine kinase, SH3 domain, Cell Line, Phosphates, Nucleotide exchange factor, Mice, Cytosol, Dogs, Proto-Oncogene Proteins, Anti-apoptotic Ras signalling cascade, parasitic diseases, Animals, Guanine Nucleotide Exchange Factors, Humans, Phosphorylation, Protein Precursors, Growth Substances, Molecular Biology, Adaptor Proteins, Signal Transducing, GRB2 Adaptor Protein, biology, Hepatocyte Growth Factor, Macrophages, Cell Membrane, Proteins, Receptor Protein-Tyrosine Kinases, Signal transducing adaptor protein, Cell Biology, Molecular biology, Recombinant Proteins, Enzyme Activation, ErbB Receptors, Kinetics, ras Proteins, biology.protein, ras Guanine Nucleotide Exchange Factors, Guanosine Triphosphate, GRB2, Signal transduction
Abstract

Macrophage-stimulating protein (MSP) is a chemotactic factor that activates the receptor tyrosine kinase RON. The involvement of Ras in MSP-induced signal transduction was investigated. Here we demonstrate that, in RON-transfected MDCK cells, an active GTP-bound form of Ras was rapidly accumulated by MSP treatment and the Ras-guanine nucleotide exchange activity in SOS immunoprecipitates was concomitantly increased. GAP activity was not changed under the same conditions used. Furthermore, the SH2 domain of adaptor protein GRB2 but not Shc, associated with the activated RON-β chain, and GRB2-SOS complexes translocated from the cytosol to the membrane upon MSP treatment. These results strongly suggest that MSP activates Ras through RON, and that MSP-induced activation of Pas might be controlled by both the enhancement of catalytic exchange activity of SOS and its translocation to the membrane where its target Ras is localized.

Published
1995

5. A novel putative receptor protein tyrosine kinase of the met family

Author

C, Ronsin, F, Muscatelli, M G, Mattei, and R, Breathnach

Subjects
Base Sequence, Molecular Sequence Data, Chromosome Mapping, Gene Expression, Receptor Protein-Tyrosine Kinases, Receptors, Cell Surface, DNA, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-met, Proto-Oncogene Mas, Cell Line, Proto-Oncogene Proteins, Humans, Amino Acid Sequence, Chromosomes, Human, Pair 3
Abstract

By successive screenings of cDNA libraries prepared from human tumours and from human foreskin keratinocytes, we have isolated overlapping cDNAs coding for a novel protein which we call Ron, with sequence characteristics of a receptor protein tyrosine kinase. Ron is a 1400 amino acid protein structurally similar to the 1408 amino acid product of the C-MET proto-oncogene, the receptor for hepatocyte growth factor and scatter factor. The two proteins have 63% overall sequence identity in their intracellular regions. We have localised the RON gene to human chromosome region 3p21, a region frequently deleted in small cell carcinoma of the lung and in renal cell carcinoma, and which is believed to harbour unidentified tumour suppressor genes. Interestingly, normal lung tissue contains transcripts of the RON gene.

Published
1993

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