Identification of the ron gene product as the receptor for the human macrophage stimulating protein

Science. 1994 Oct 7;266(5182):117-9. doi: 10.1126/science.7939629.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Cross-Linking Reagents
  • Growth Substances
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • macrophage stimulating protein
  • Hepatocyte Growth Factor
  • Plasminogen
  • RON protein
  • Receptor Protein-Tyrosine Kinases