Mouse Hepatocyte Growth Factor (HGF) Activator Inhibitor Type 2 Lacking the First Kunitz Domain Potently Inhibits the HGF Activator
| Autor: | Ryouichi Hamasuna, Takeshi Shimomura, Naomi Kitamura, Yoshitsugu Nuki, Hiroshi Itoh, Seiji Naganuma, Hiroaki Kataoka |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Serine Proteinase Inhibitors
animal structures medicine.medical_treatment Molecular Sequence Data Biophysics CHO Cells Hepatocyte Growth Factor Activator Biology Transfection Biochemistry law.invention Serine Mice law Cricetinae medicine Animals Humans Amino Acid Sequence RNA Messenger Molecular Biology Plant Proteins Membrane Glycoproteins Dose-Response Relationship Drug Sequence Homology Amino Acid Growth factor Chinese hamster ovary cell Serine Endopeptidases virus diseases Cell Biology Molecular biology Mutation RNA splicing Recombinant DNA Hepatocyte growth factor Trypsin Inhibitor Kunitz Soybean Kunitz domain Peptides Trypsin Inhibitors medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 290:1096-1100 |
| ISSN: | 0006-291X |
| DOI: | 10.1006/bbrc.2001.6313 |
| Popis: | Hepatocyte growth factor activator inhibitor type 2 (HAI-2) is a serine proteinase inhibitor containing two Kunitz-type inhibitor domains, initially identified as a potent inhibitor of hepatocyte growth factor activator (HGFA). In a previous study (Biochem. Biophys. Res. Commun. 255, 740-748, 1999), we reported that a predominant transcript of mouse HAI-2 is a splicing variant lacking the first Kunitz domain (KD-1). Since KD-1 was reported to be responsible for the inhibition of HGFA in human HAI-2 and the second Kunitz domain (KD-2) of human HAI-2 was much less inhibitory against HGFA, it has been suggested that most of mouse HAI-2 may be ineffective in inhibiting HGFA. In this study, we have performed functional characterization of Kunitz domains in mouse HAI-2 by using recombinant proteins synthesized by Chinese hamster ovary cells without or with point mutation in the putative reactive site of each Kunitz domain. The results revealed that, unlike human HAI-2, KD-2 of mouse HAI-2 efficiently inhibits HGFA. Therefore, the major mouse HAI-2 protein that consists only of KD-2 can be a potent inhibitor of HGF activation in vivo. |
| Databáze: | OpenAIRE |
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