Effect of purified, soluble urokinase receptor on the plasminogen-prourokinase activation system.
The extracellular proteolytic pathway mediated by the urokinase plasminogen activator (uPA) is a cascade system, initiated by activation of the zymogen, pro-uPA. Pro-uPA as well as uPA binds to the cellular uPA receptor (uPAR) which has a central function in cell-dependent acceleration of the cascade system. This role of uPAR is generally assumed to be a positioning effect since uPAR-expressing cells exclusively stimulate the activation of cell surface-bound plasminogen (Ellis et al. (1993) 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 accelerative role. In contrast, the progress of the activation reactions in a soluble system with pro-uPA and plasminogen was found to be attenuated by suPAR. This delay of the activation system was shown to include a partial inhibition of the plasmin-mediated activation of pro-uPA as well as of the uPA-mediated activation of plasminogen.
Behrendt
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Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark. ged@biobase.dk
Danø
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D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D006801:Humans; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
C524898:PLAUR protein, human; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D010958:Plasminogen; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator