Inhibition of Membrane-Type Serine Protease 1/Matriptase by Natural and Synthetic Protease Inhibitors
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概要
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Membrane-type serine protease 1 (MT SP1), identical to matriptase, is a recently identified type II transmembrane serine protease. MT-SP 1/matriptase is of consider-able interest for the development, homeostasis, and cancer invasion and metastasis of epithelial tissues. The administration of inhibitors for MT SP 1/matriptase may be effective to suppress the development of tumors where the enzyme may be involved. In the present study, we produced a secreted form of recombinant MT SP 1/matriptase (ekMT-SP1s) that can be activated by enterokinase in vitro and investigated the inhibitory ability of various protease inhibitors toward the recombinant enzyme. The enterokinase-treated ekMT-SP1s (active ekMT-SP1s) cleaved various peptidyl-4-methylcoumaryl-7-amide (MCA) substrates with arginine (or lysine) residue at position P1, and the best substrate was t-butyloxycar-bonyl (Boc)-Gln-Ala-Arg-MCA. The specificity for the synthetic and natural substrates of the active ekMT-SP1s was in good agreement with that of the natural enzyme. Endogenous protease inhibitors tested, except for antithrombin III, showed no or little inhibition on the cleavage of Boc-Gln-Ala-Arg-MCA by the active ekMT-SP1s. Aprotinin showed strong in-hibitory activity toward the cleavage. Food-derived inhibitors, such as soybean trypsin in-hibitor, Bowman-Birk inhibitor, and lima bean trypsin inhibitor inhibited it, while chicken ovomucoid did not. Synthetic inhibitors tested inhibited it, and among them, the inhibitory effect of FOY 305 was strongest. The present findings provide important information for the suppression of cancer invasion and metastasis for which MT-SP1/matriptase is responsible.
- 財団法人 学会誌刊行センターの論文
- 2003-02-01
著者
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Fushiki Tohru
Kyoto Univ. Kyoto City Jpn
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Tsuzuki Satoshi
Laboratory Of Nutrition Chemistry Division Of Food Science And Biotechnology Graduate School Of Agri
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Murai Nobuhito
Laboratory Of Nutrition Chemistry Division Of Food Science And Biotechnology Graduate School Of Agri
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Fushiki Tohru
Laboratory Of Nutrition Chemistry Division Of Food Science And Biotechnology Graduate School Of Agri
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Fushiki Tohru
Laboratory Of Nutrition Chemistry Division Of Food Science And Biotechnology Graduate School Of Agri
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Fushiki Tohru
Laboratory Of Nutrition Chemistry Division Of Applied Life Sciences Graduate School Of Agriculture K
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Satomi Shigeki
Laboratory Of Nutrition Chemistry Division Of Food Science And Biotechnology Graduate School Of Agri
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Yamasaki Yoshie
Laboratory Of Nutrition Chemistry Division Of Food Science And Biotechnology Graduate School Of Agri
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Yamasaki Yoshie
Laboratory Of Nutrition Chemistry Division Of Food Science And Biotechnology Graduate School Of Agri
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Satomi Shigeki
Laboratory Of Nutrition Chemistry Division Of Food Science And Biotechnology Graduate School Of Agri
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