Functional characterization of Kunitz domains in hepatocyte growth factor activator inhibitor type 2.
Hepatocyte growth factor activator inhibitor type 2 (HAI-2) was identified as a potent inhibitor of hepatocyte growth factor activator (HGF activator). The primary translation product of HAI-2 contains two Kunitz domains. To characterize their function, we introduced a point mutation into the reactive site of each Kunitz domain, and assayed the mutants for their HGF activator inhibitory activity. A point mutation in the COOH-terminal Kunitz domain did not affect the activity of HAI-2, whereas a point mutation in the NH2-terminal Kunitz domain markedly reduced the activity. These results suggest that the NH2-terminal Kunitz domain is mainly responsible for the HGF activator inhibitory activity of HAI-2.
Department of Life Science, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta, Yokohama, Japan.
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L
Qin
K
K
Denda
T
T
Shimomura
T
T
Kawaguchi
N
N
Kitamura
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D018076:DNA, Complementary; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D014162:Transfection; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000378:metabolism*
D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C109148:SPINT2 protein, human; D014360:Trypsin Inhibitor, Kunitz Soybean; C081092:HGF activator; D012697:Serine Endopeptidases