tailieunhanh - Báo cáo khoa học: TMPRSS13, a type II transmembrane serine protease, is inhibited by hepatocyte growth factor activator inhibitor type 1 and activates pro-hepatocyte growth factor

Type II transmembrane serine proteases (TTSPs) are structurally defined by the presence of a transmembrane domain located near the N-terminus and a C-terminal extracellular serine protease domain. The human TTSP family consists of 17 members. Some members of the family have pivotal functions in development and homeostasis, and are involved in tumorigene-sis and viral infections. | TMPRSS13 a type II transmembrane serine protease is inhibited by hepatocyte growth factor activator inhibitor type 1 and activates pro-hepatocyte growth factor Tomio Hashimoto1 Minoru Kato2 Takeshi Shimomura2 and Naomi Kitamura1 1 Department of BiologicalSciences Graduate Schoolof Bioscience and Biotechnology Tokyo Institute of Technology Nagatsuta Midori-ku Yokohama Japan 2 Advanced MedicalResearch Laboratory Mitsubishi Tanabe Pharma Corporation Kamoshida-cho Aoba-ku Yokohama Japan Keywords activation of pro-hepatocyte growth factor hepatocyte growth factor activator inhibitor type 1 HAI-1 Kunitz-type inhibitor TMPRSS13 type II transmembrane serine protease TTSP Correspondence N. Kitamura Department of Biological Sciences Graduate School of Bioscience and Biotechnology Tokyo Institute of Technology Nagatsuta Midori-ku Yokohama 226-8501 Japan Fax 81 45 924 5771 Tel 81 45 924 5701 E-mail nkitamur@ Received 31 May 2010 revised 26 August 2010 accepted 24 September 2010 doi Type II transmembrane serine proteases TTSPs are structurally defined by the presence of a transmembrane domain located near the N-terminus and a C-terminal extracellular serine protease domain. The human TTSP family consists of 17 members. Some members of the family have pivotal functions in development and homeostasis and are involved in tumorigene-sis and viral infections. The activities of TTSPs are regulated by endogenous protease inhibitors. However protease inhibitors of most TTSPs have not yet been identified. In this study we investigated the inhibitory effect of hepatocyte growth factor activator inhibitor type 1 HAI-1 a Kunitz-type serine protease inhibitor on several members of the TTSP family. We found that the protease activity of a member TMPRSS13 was inhibited by HAI-1. A detailed analysis revealed that a soluble form of HAI-1 with one Kunitz domain NK1 more strongly inhibited TMPRSS13 than another soluble form of HAI-1 with two Kunitz