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 alpha1) 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 alpha1 could contribute to fibrin stimulation irrespective of fibrin binding. We now demonstrate that the protease domain of D. rotundus PA alpha1 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 alpha1 and t-PA.
Toschi
L
L
Research Laboratories of Schering AG Berlin, Germany. luisella.toschi@schering.de
Bringmann
P
P
Petri
T
T
Donner
P
P
Schleuning
W D
WD
D000818:Animals; D002685:Chiroptera; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects*; D005337:Fibrin / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology; D007700:Kinetics; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D010446:Peptide Fragments; D011994:Recombinant Proteins; C069588:salivary plasminogen activator alpha 1, Desmodus rotundus; D005337:Fibrin; D005340:Fibrinogen; D010450:Endopeptidases; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator