Identification of the Novel Plasminogen Receptor, Plg-RKT

1.1 The plasminogen activation system Initiation of the plasminogen activation system results in generation of the broad spectrum serine protease, plasmin, from the circulating zymogen, plasminogen. Plasminogen is activated to plasmin by plasminogen activators (PA’s), either urokinase type-plasminogen activator (u-PA) or tissue-type plasminogen activator (t-PA), via specific proteolytic cleavage (Castellino & Ploplis, 2005). Plasmin is the major enzyme responsible for degradation of fibrin clots (fibrinolysis) to maintain normal blood homeostasis (Bugge et al., 1995; Ploplis et al., 1995). Dysregulation of the plasminogen activation system can result in hemorrhage (excess fibrinolysis) or thrombosis (insufficient fibrinolysis). The plasminogen activation system is regulated by direct inhibition of plasmin (by the circulating serpin, ┙2antiplasmin) and by synthesis and secretion of plasminogen activators and the serpin, plasminogen activator inhibitor 1 (PAI-1)] (Collen, 1999). In a key regulatory step, plasminogen activation is promoted when plasminogen and its activator, t-PA, bind concomitantly to lysine residues on the surface of fibrin clots, resulting in a marked reduction in the Km for activation of plasminogen compared with the reaction in solution (Hoylaerts et al., 1982).