EFFECT OF PURIFIED, SOLUBLE UROKINASE RECEPTOR ON THE PLASMINOGEN-PROUROKINASE ACTIVATION SYSTEM

The extracellular proteolytic pathway mediated by the urokinase plasmi nogen activator (uPA) is a cascade system, initiated by activation of the zymogen, pro-uPA, Pro-uPA as web as uPA binds to the cellular uPA receptor (uPAR),which has a central function in cell-dependent acceler ation of the cascade system. This role of uPAR is generally assumed to be a positioning effect since uPAR-expressing cells exclusively stimu late the activation of cell surface-bound plasminogen (Ellis et al. (1 993) Methods Enzymol. 223, 223-233), However, it was recently reported that a recombinant, soluble uPAR (suPAR) was capable of accelerating plasminogen activation in solution (Higazi et al. (1995) J. Biol. Chem . 270, 17375-17380), In this work we show that suPAR as such has no ac celerative role. In contrast, the progress of the activation reactions in a soluble system with pro-uPA and plasminogen was found to be atte nuated by suPAR, This delay of the activation system was shown to incl ude a partial inhibition of the plasmin-mediated activation of pro-uPA as web as of the uPA-mediated activation of plasminogen.