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 activator (D. rotundus PA alpha 1) and to a much lesser extent of tissue-type plasminogen activator (t-PA) is stimulated by the presence of fibrin. This cofactor requirement has in the past intuitively been attributed to fibrin binding. We have previously shown that elements of the non-protease domain of D. rotundus PA alpha 1 could contribute to fibrin stimulation irrespective of fibrin binding. We now demonstrate that the protease domain of D. rotundus PA alpha 1 by itself exhibits fibrin 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 protein-protein interactions apart from fibrin binding affect the stimulatory mechanism of fibrin on D. rotundus PA alpha 1 and t-PA.