Identification of the ron Gene Product as the Receptor for the Human Macrophage Stimulating Protein

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 $^{125}$I-labeled MS...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1994-10, Vol.266 (5182), p.117-119
Main Authors: Wang, Ming-Hai, Ronsin, Christophe, Gesnel, Marie-Claude, Coupey, Lionel, Skeel, Alison, Leonard, Edward J., Breathnach, Richard
Format: Article
Language:English
Subjects:
3T3 cells
Animals
Antibodies
Binding Sites
Binding, Competitive
Biological and medical sciences
Cell Line
Cell membranes
Cell Movement - drug effects
Cellular immunity
Complementary DNA
Cross-Linking Reagents
Dogs
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Growth Substances - metabolism
Growth Substances - pharmacology
Hepatocyte Growth Factor - metabolism
Hepatocytes
Humans
Immunobiology
Immunopathology
Immunoprecipitation
Macrophage colony stimulating factor
Macrophages
Monocytes, macrophages
Myeloid cells: ontogeny, maturation, markers, receptors
Phosphorylation
Plasminogen - metabolism
Proto-Oncogene Proteins
Receptor Protein-Tyrosine Kinases - genetics
Receptor Protein-Tyrosine Kinases - metabolism
Receptors
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Transfection
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Summary: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 $^{125}$I-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 β chain of Ron (150 kilodaltons). The binding of $^{125}$I-labeled MSP to MDCK-RE7 cells was inhibited by unlabeled MSP, but not by HGF-SF. MSP caused phosphorylation of the β 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.7939629