FUNCTIONAL-ANALYSIS OF THE CELLULAR RECEPTOR FOR UROKINASE IN PLASMINOGEN ACTIVATION - RECEPTOR BINDING HAS NO INFLUENCE ON THE ZYMOGENIC NATURE OF PRO-UROKINASE

Plasminogen activation catalyzed by the urokinase-type plasminogen act ivator (uPA) constitutes a reciprocal zymogen activation system, as pl asmin can efficiently activate pro-uPA, the single-chain zymogenic for m of the protease, We have previously shown that the overall efficienc y of this plasminogen activation system is greatly enhanced by its ass embly on the cell surface, involving binding of pro-uPA to its cellula r binding site uPAR, and the concurrent cellular binding of plasminoge n. We have now studied the effect of a recombinant soluble form of uPA R (residues 1-277) on the proteolytic reactions of this system. In con trast to the increased efficiencies of plasminogen activation and pro- uPA activation observed with cell-surface uPAR, soluble uPAR had an in hibitory effect on both of these individual reactions, Soluble uPAR al so caused no increase in the low, but discernible, intrinsic activity of pro-uPA, Consistent with the observations on the isolated reactions , the overall activity of the pro-uPA-mediated plasminogen activation system was significantly inhibited. These observations confirm the pre vious interpretation of the observations made with cell-surface uPAR t hat the mechanism of the enhanced plasmin generation is due to the cat alytically favorable interaction of uPAR-bound uPA/pro-uPA with cell-b ound plasminogen/plasmin, rather than direct effects on the properties of uPA or pro-uPA on binding to uPAR.