Proteolytic activation of a single-chain precursor of hepatocyte growth factor by extracellular serine-protease

Kensaku Mizuno, Toyohiro Takehara, Toshikazu Nakamura

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Hepatocyte growth factor (HGF) is biosynthesized as a single-chain precursor (pro-HGF) and is proteolytically processed to a two-chain mature form. When MRC-5 fibroblasts were pulse-radiolabeled under serum-free conditions, pro-HGF was the predominant molecular form of HGF in the culture medium. CHO cells transfected with an expression plasmid containing a full-size human HGF cDNA produced pro-HGF when these cells were cultured in serum-free medium. These findings suggest that HGF is secreted as a pro-form, which is then converted to a two-chain form by extracellular protease. Single-chain HGF exhibited mitogenic activity on cultured hepatocytes, with a potency similar to that of mature HGF, but this activity was remarkably inhibited by leupeptin. We postulate that inactive pro-HGF is converted to an active two-chain form by a leupeptin-sensitive serine-protease expressed by hepatocytes. Neither plasminogen activators nor plasmin showed any processing activity of pro-HGF in vitro.

Original languageEnglish
Pages (from-to)1631-1638
Number of pages8
JournalBiochemical and biophysical research communications
Volume189
Issue number3
DOIs
Publication statusPublished - 1992 Dec 30
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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