DOI: 10.1126/science.7939629. Identification of the <i>ron</i> Gene Product as the Receptor for the Human Macrophage Stimulating Protein

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

10.1126/science.7939629

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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 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.

Bibliography

Wang, M.-H., Ronsin, C., Gesnel, M.-C., Coupey, L., Skeel, A., Leonard, E. J., & Breathnach, R. (1994). Identification of the ron Gene Product as the Receptor for the Human Macrophage Stimulating Protein. Science, 266(5182), 117â119.

Authors 7

Ming-Hai Wang (first)
Christophe Ronsin (additional)
Marie-Claude Gesnel (additional)
Lionel Coupey (additional)
Alison Skeel (additional)
Edward J. Leonard (additional)
Richard Breathnach (additional)

References 25 Referenced 212

10.1126/science.1846706
10.1056/NEJM198710293171803
DEAN, M, THE HUMAN MET ONCOGENE IS RELATED TO THE TYROSINE KINASE ONCOGENES, NATURE 318: 385 (1985). (10.1038/318385a0) / NATURE (1985)
HAN, S, CHARACTERIZATION OF THE DNF15S2 LOCUS ON HUMAN-CHROMOSOME .3. IDENTIFICATION OF A GENE CODING FOR 4 KRINGLE DOMAINS WITH HOMOLOGY TO HEPATOCYTE GROWTH-FACTOR, BIOCHEMISTRY 30: 9768 (1991). (10.1021/bi00104a029) / BIOCHEMISTRY (1991)
HUFF, J.L., THE PROTOONCOGENE C-SEA ENCODES A TRANSMEMBRANE PROTEIN-TYROSINE KINASE RELATED TO THE MET HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-RECEPTOR, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90: 6140 (1993). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1993)
LANE K unpublished data.
LEONARD, E.J., SERUM-PROTEIN THAT STIMULATES MACROPHAGE MOVEMENT, CHEMOTAXIS AND SPREADING, EXPERIMENTAL CELL RESEARCH 102: 434 (1976). (10.1016/0014-4827(76)90065-3) / EXPERIMENTAL CELL RESEARCH (1976)
LEONARD, E.J., ISOLATION OF MACROPHAGE STIMULATING PROTEIN (MSP) FROM HUMAN-SERUM, EXPERIMENTAL CELL RESEARCH 114: 117 (1978). (10.1016/0014-4827(78)90043-5) / EXPERIMENTAL CELL RESEARCH (1978)
MATSUMOTO, K, CRIT REV ONCOGEN 3: 27 (1992). / CRIT REV ONCOGEN (1992)
NAKAMURA, T, MOLECULAR-CLONING AND EXPRESSION OF HUMAN HEPATOCYTE GROWTH-FACTOR, NATURE 342: 440 (1989). (10.1038/342440a0) / NATURE (1989)
NALDINI, L, HEPATOCYTE GROWTH-FACTOR (HGF) STIMULATES THE TYROSINE KINASE-ACTIVITY OF THE RECEPTOR ENCODED BY THE PROTOONCOGENE C-MET, ONCOGENE 6: 501 (1991). / ONCOGENE (1991)
PATTHY, L, KRINGLES - MODULES SPECIALIZED FOR PROTEIN-BINDING HOMOLOGY OF THE GELATIN-BINDING REGION OF FIBRONECTIN WITH THE KRINGLE STRUCTURES OF PROTEASES, FEBS LETTERS 171: 131 (1984). (10.1016/0014-5793(84)80473-1) / FEBS LETTERS (1984)
RONG, S, TUMORIGENICITY OF THE MET PROTOONCOGENE AND THE GENE FOR HEPATOCYTE GROWTH-FACTOR, MOLECULAR AND CELLULAR BIOLOGY 12: 5152 (1992). / MOLECULAR AND CELLULAR BIOLOGY (1992)
RONSIN, C, A NOVEL PUTATIVE RECEPTOR PROTEIN TYROSINE KINASE OF THE MET FAMILY, ONCOGENE 8: 1195 (1993). / ONCOGENE (1993)
RONSIN C unpublished data.
RUBIN, J.S., HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR AND ITS RECEPTOR, THE C-MET PROTOONCOGENE PRODUCT, BIOCHIMICA ET BIOPHYSICA ACTA 1155: 357 (1993). / BIOCHIMICA ET BIOPHYSICA ACTA (1993)
SKEEL, A, MACROPHAGE STIMULATING PROTEIN - PURIFICATION, PARTIAL AMINO-ACID-SEQUENCE, AND CELLULAR-ACTIVITY, JOURNAL OF EXPERIMENTAL MEDICINE 173: 1227 (1991). (10.1084/jem.173.5.1227) / JOURNAL OF EXPERIMENTAL MEDICINE (1991)
SKEEL, A, ACTION AND TARGET-CELL SPECIFICITY OF HUMAN MACROPHAGE-STIMULATING PROTEIN (MSP), JOURNAL OF IMMUNOLOGY 152: 4618 (1994). (10.4049/jimmunol.152.9.4618) / JOURNAL OF IMMUNOLOGY (1994)
STOKER, M, SCATTER FACTOR IS A FIBROBLAST-DERIVED MODULATOR OF EPITHELIAL-CELL MOBILITY, NATURE 327: 239 (1987). (10.1038/327239a0) / NATURE (1987)
WANG, M.H., PROTEOLYTIC CONVERSION OF SINGLE-CHAIN PRECURSOR MACROPHAGE-STIMULATING PROTEIN TO A BIOLOGICALLY-ACTIVE HETERODIMER BY CONTACT ENZYMES OF THE COAGULATION CASCADE, JOURNAL OF BIOLOGICAL CHEMISTRY 269: 3436 (1994). (10.1016/S0021-9258(17)41881-3) / JOURNAL OF BIOLOGICAL CHEMISTRY (1994)
WANG, M.H., PROTEOLYTIC ACTIVATION OF SINGLE-CHAIN PRECURSOR MACROPHAGE-STIMULATING PROTEIN BY NERVE GROWTH FACTOR-GAMMA AND EPIDERMAL GROWTH FACTOR-BINDING PROTEIN, MEMBERS OF THE KALLIKREIN FAMILY, JOURNAL OF BIOLOGICAL CHEMISTRY 269: 13806 (1994). (10.1016/S0021-9258(17)36719-4) / JOURNAL OF BIOLOGICAL CHEMISTRY (1994)
WANG, M.H., MACROPHAGE-STIMULATING PROTEIN INHIBITS INDUCTION OF NITRIC-OXIDE PRODUCTION BY ENDOTOXIN-STIMULATED OR CYTOKINE-STIMULATED MOUSE MACROPHAGES, JOURNAL OF BIOLOGICAL CHEMISTRY 269: 14027 (1994). (10.1016/S0021-9258(17)36750-9) / JOURNAL OF BIOLOGICAL CHEMISTRY (1994)
WEIDNER, K.M., EVIDENCE FOR THE IDENTITY OF HUMAN SCATTER FACTOR AND HUMAN HEPATOCYTE GROWTH-FACTOR, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88: 7001 (1991). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1991)
YOSHIMURA, T, CLONING, SEQUENCING, AND EXPRESSION OF HUMAN MACROPHAGE STIMULATING PROTEIN (MSP, MST1) CONFIRMS MSP AS A MEMBER OF THE FAMILY OF KRINGLE PROTEINS AND LOCATES THE MSP GENE ON CHROMOSOME-3, JOURNAL OF BIOLOGICAL CHEMISTRY 268: 15461 (1993). (10.1016/S0021-9258(18)82279-7) / JOURNAL OF BIOLOGICAL CHEMISTRY (1993)
10.1038/327721a0

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 8:01 p.m.)
Deposited	1 year, 7 months ago (Jan. 14, 2024, 11:17 p.m.)
Indexed	1 month, 1 week ago (July 22, 2025, 7:16 a.m.)
Issued	30 years, 10 months ago (Oct. 7, 1994)
Published	30 years, 10 months ago (Oct. 7, 1994)
Published Print	30 years, 10 months ago (Oct. 7, 1994)

Funders 0

None

BibTeX

@article{Wang_1994, title={Identification of the ron Gene Product as the Receptor for the Human Macrophage Stimulating Protein}, volume={266}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.7939629}, DOI={10.1126/science.7939629}, number={5182}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Wang, Ming-Hai and Ronsin, Christophe and Gesnel, Marie-Claude and Coupey, Lionel and Skeel, Alison and Leonard, Edward J. and Breathnach, Richard}, year={1994}, month=oct, pages={117–119} }

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  },
  "alternative-id": [
    "10.1126/science.7939629"
  ],
  "URL": "http://dx.doi.org/10.1126/science.7939629",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1994,
        10,
        7
      ]
    ]
  }
}