A fibroblast-derived urokinase-inhibitor differing from protease nexin

UK-I, a 60-kDa urokinase-inhibitor derived from human fibroblasts, inhibited 54-kDa urokinase (EC 3.4.21.31) activity dose-dependently on ordinary fibrin-agar autograms. This UK-I formed an SDS-stable approximately 75-kDa complex with radioiodinated urokinase (33 kDa) on an autoradiogram following SDS/polyacrylamide gel electrophoresis. Benzamidine hydrochloride inhibited its formation, indicating UK-I to bind at the active site of urokinase and form an inactive complex. UK-I did not form a complex with [125I]thrombin (EC 3.4.21.5). It is thus evident that UK-I is one type of urokinase-inhibitor derived from human fibroblasts with properties differing from protease nexin, another urokinase-inhibitor derived from the same source.