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

L. Naldini, E. Vigna, R. P. Narsimhan, G. Gaudino, R. Zarnegar, G. K. Michalopoulos, P. M. Comoglio

Research output: Contribution to journalArticle

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 p 190c-met. Moreover, elution of immunoprecipitates obtained with antiMET 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.

Original languageEnglish
Pages (from-to)501-504
Number of pages4
JournalOncogene
Volume6
Issue number4
Publication statusPublished - Apr 1991

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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    Naldini, L., Vigna, E., Narsimhan, R. P., Gaudino, G., Zarnegar, R., Michalopoulos, G. K., & Comoglio, P. M. (1991). Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET. Oncogene, 6(4), 501-504.