ACTIVATION OF HEPATOCYTE GROWTH-FACTOR BY 2 HOMOLOGOUS PROTEASES, BLOOD-COAGULATION FACTOR-XIIA AND HEPATOCYTE GROWTH-FACTOR ACTIVATOR

Hepatocyte growth factor (HGF) is secreted as an inactive single-chain precursor from the producing cells, and normally remains in this form associated with the extracellular matrix. In response to tissue injur y, the single-chain precursor is converted to a biologically active he terodimer by a serine protease, the activity of which is induced in th e injured tissue. We have previously identified HGF activator, a serum serine protease that activates single-chain HGF. The sequence of HGF activator cDNA revealed that the HGF activator is homologous to blood- coagulation factor XIIa. In this study, we found that coagulation fact or XIIa has an ability to activate single-chain HGF. Factor XIIa exhib ited a significant level of HGF-converting activity in the presence of dextran sulfate, although the specific activity of factor XIIa was sl ightly lower than that of the HGF activator. Since factor XIIa is acti vated during the initiation of contact activation induced by tissue in jury, factor XIIa may function as an HGF-converting enzyme together wi th HGF activator in the injured tissue. C1-inhibitor, antithrombin III and alpha(2)-antiplasmin, that regulate the blood-clotting activity o f factor XIIa, were also effective against the HGF-converting activity of factor XIIa. Furthermore, factor XIIa was not active in the HGF-co nverting activity in serum. Thus, the HGF-converting activity of facto r XIIa may be regulated by these serum inhibitors.