FIBRIN SELECTIVITY OF THE ISOLATED PROTEASE DOMAINS OF TISSUE-TYPE AND VAMPIRE BAT SALIVARY-GLAND PLASMINOGEN ACTIVATORS

The activity of vampire bat (Desmodus rotundus) salivary plasminogen a ctivator (D. rotundus PA alpha 1) and to a much lesser extent of tissu e-type plasminogen activator (t-PA) is stimulated by the presence of f ibrin. This cofactor requirement has in the past intuitively been attr ibuted to fibrin binding. We have previously shown that elements of th e non-protease domain of D. rotundus PA alpha 1 could contribute to fi brin stimulation irrespective of fibrin binding.We now demonstrate tha t the protease domain of D. rotundus PA alpha 1 by itself exhibits fib rin selectivity, i.e. it is 32-fold stimulated by fibrin but only 1.5- fold by fibrinogen. To a lesser extent this fibrin selectivity is also shared by the protease domain of t-PA. Our findings indicate that pro tein-protein interactions apart from fibrin binding affect the stimula tory mechanism of fibrin on D. rotundus PA alpha 1 and t-PA.