title: Mouse hepatocyte growth factor (HGF) activator inhibitor type 2 lacking the first Kunitz domain potently inhibits the HGF activator.
abstract: 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.
authors.affiliation: Second Department of Pathology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kataoka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Nuki
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Hamasuna
authors.forename: Seiji
authors.initials: S
authors.lastname: Naganuma
authors.forename: Naomi
authors.initials: N
authors.lastname: Kitamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimomura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides; D010940:Plant Proteins; D012333:RNA, Messenger / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D014162:Transfection; D014360:Trypsin Inhibitor, Kunitz Soybean; D014361:Trypsin Inhibitors / Q000737:chemistry
chemical_list: C053865:Kunitz-type protease inhibitor, plant; D008562:Membrane Glycoproteins; D010455:Peptides; D010940:Plant Proteins; D012333:RNA, Messenger; C109148:SPINT2 protein, human; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D014360:Trypsin Inhibitor, Kunitz Soybean; C081092:HGF activator; D012697:Serine Endopeptidases