Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET

Oncogene. 1991 Apr;6(4):501-4.

Abstract

The human proto-oncogene c-MET encodes a heterodimeric 190 kDa transmembrane protein (p190c-met) with structural features of a tyrosine kinase receptor. The ligand for this putative receptor has not yet been identified. By Northern blot hybridization we found that, among a restricted number of human tissues, c-MET is highly expressed in the liver. This prompted us to test the hypothesis of a functional interaction between the c-MET receptor and Hepatocyte Growth Factor (HGF), a heparin-binding polypeptide consisting of heavy and light chains of 65 and 35 kDa. Nanomolar concentrations of highly purified HGF added to GTL-16 cells, which overexpress the c-MET receptor, enhanced the phosphorylation on tyrosine of the p190c-met kinase. Addition of other known growth factors or serum was ineffective. The kinase activity of the c-MET receptor was also stimulated by HGF in an in vitro assay, after detergent solubilization and partial purification of p190c-met. Moreover, elution of immunoprecipitates obtained with anti-MET antibodies from GTL-16 cell lysates yielded an HGF-responsive kinase activity. These results suggest that HGF, or a growth factor structurally related to HGF, is a candidate ligand for the receptor encoded by c-MET.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Glands / metabolism
  • ErbB Receptors / metabolism*
  • Female
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation
  • Growth Substances / physiology*
  • Hepatocyte Growth Factor
  • Humans
  • In Vitro Techniques
  • Kidney / metabolism
  • Liver / metabolism
  • Lung / metabolism
  • Ovary / metabolism
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / biosynthesis*
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-met
  • RNA, Messenger / biosynthesis
  • Spleen / metabolism
  • Thyroid Gland / metabolism
  • Uterus / metabolism

Substances

  • Growth Substances
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Hepatocyte Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-met