FIBRIN AFFINITY OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR - EVIDENCE THAT ZN2-CHAIN UROKINASE WITH FIBRIN( MEDIATES STRONG AND SPECIFIC INTERACTION OF SINGLE)

Interactions of components of the fibrinolytic system with fibrin play a key role in localization and regulation of plasminogen activation a t the clot surface. Although interaction of tissue plasminogen activat or (tPA) with fibrin is well established, the prevailing view is that urokinase-type plasminogen activator (uPA) does not bind to fibrin. In this report, I show that although there is little or no interaction o f single-chain urokinase (Sc-uPA), two-chain urokinase (Tc-uPA), or lo w molecular weight urokinase (LMW-uPA) with fibrin in the absence of d ivalent metal cations, Sc-uPA is effectively bound to fibrin in the pr esence of Zn2+. By comparison, Tc-uPA is poorly bound and LMW-uPA is n ot bound to fibrin in the presence of the metal ion. The Zn2+-mediated fibrin binding of Sc-uPA is reversible, specific, and saturable. The interaction involves a single class of binding site with dissociation constant of 0.3 muM and stoichiometry of 2.7. Lacking apparent affinit y for fibrin, uPA has not been considered to play a role in physiologi cal fibrinolysis. The present study conclusively shows that Sc-uPA pos sesses a latent affinity for fibrin that is expressed in the presence of Zn2+. These findings raise the possibility that Zn2+ plays a regula tory role in uPA-mediated fibrinolysis by promoting effective localiza tion of Sc-uPA at the clot surface.