FUNCTIONAL-CHARACTERIZATION OF KUNITZ DOMAINS IN HEPATOCYTE GROWTH-FACTOR ACTIVATOR INHIBITOR TYPE-2

Hepatocyte growth factor activator inhibitor type 2 (HAI-2) was identi fied as a potent inhibitor of hepatocyte growth factor activator (HGF activator). The primary translation product of HAI-2 contains two Kuni tz domains. To characterize their function, we introduced a point muta tion into the reactive site of each Kunitz domain, and assayed the mut ants 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 re duced the activity. These results suggest that the NH2-terminal Kunitz domain is mainly responsible for the HGF activator inhibitory activit y of HAI-2. (C) 1998 Federation of European Biochemical Societies.