HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor

FEBS Lett. 1997 Dec 22;420(1):1-6. doi: 10.1016/s0014-5793(97)01475-0.


We prepared a specific antagonist for hepatocyte growth factor (HGF) and designated it HGF/NK4. HGF/NK4 is composed of N-terminal 447 amino acids of the alpha-chain of HGF, thus contains the N-terminal hairpin domain and subsequent four kringle domains. HGF/NK4 competitively inhibited the specific binding of HGF to the receptor. Importantly, HGF/NK4 neither stimulated DNA synthesis of primary cultured rat hepatocytes (mitogenesis) nor induced cell scattering (motogenesis) and branching tubulogenesis (morphogenesis) of MDCK renal epithelial cells, however, HGF/NK4 almost completely inhibited the mitogenic, motogenic, and morphogenic activities of HGF. HGF/NK4 also suppressed tyrosine phosphorylation of the c-Met/HGF receptor induced by HGF. Apparently this is the first documentation of a specific antagonist which abrogates the mitogenic, motogenic, and morphogenic activities of HGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Movement
  • Cell Size
  • Cells, Cultured
  • DNA / biosynthesis
  • Dogs
  • Hepatocyte Growth Factor / antagonists & inhibitors*
  • Hepatocyte Growth Factor / chemistry
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Kidney / cytology
  • Kringles
  • Liver / cytology
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-met / metabolism
  • Rats
  • Recombinant Proteins
  • Sequence Analysis
  • Structure-Activity Relationship
  • Tyrosine / metabolism


  • Peptide Fragments
  • Recombinant Proteins
  • Tyrosine
  • Hepatocyte Growth Factor
  • DNA
  • Proto-Oncogene Proteins c-met