Multiple Sites of Proteolytic Cleavage to Release Soluble Forms of Hepatocyte Growth Factor Activator Inhibitor Type 1 from a Transmembrane Form.
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概要
- 論文の詳細を見る
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a Kunitz-type serine protease inhibitor, which was identified as a potent inhibitor of hepatocyte growth factor (HGF) activator from the conditioned medium of a human carcinoma cell line. HGF activator is a blood coagulation factor XII-like serine protease that is responsible for proteolytic activation of the inactive single chain precursor of HGF in injured tissues. The predicted sequence of the primary translation product of HAI-1, which has a hydrophobic sequence in its COOH-terminal region, suggested that HAI-1 is first produced in a membrane-associated form. In this study, we identified a transmembrane form of HAI-1 integrated in the plasma membrane of cultured cells using a monoclonal antibody against HAI-1. We also identified several soluble forms of HAI-1 in the conditioned medium of the cells, indicating that multiple sites are present in the transmembrane form of HAI-1 at which proteolytic cleavage releases the extracellular domain. At least two proteases, one of which is a metalloprotease, appear to be responsible for the release. Further, the soluble forms of HAI-1 have different inhibitory activity against HGF activator. These findings suggest that proteolytic processing plays important roles in regulation of the inhibitory activity of HAI-1.
- 社団法人 日本生化学会の論文
著者
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Kawaguchi Toshiya
Research Center Mitsubishi Chemical Corp.
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Miyazawa Keiji
Department Of Biochemistry Interdisciplinary Graduate School Of Medicine And Engineering University
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Shimomura Takeshi
Research Center Mitsubishi Chemical Corp.
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Matsumoto Kouji
Research Center Mitsubishi Chemical Corp.
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Denda Kimitoshi
Department Of Life Science Faculty Of Bioscience And Biotechnology Tokyo Institute Of Technology
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KITAMURA NAOMI
Department of Biological Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology
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