Related Experiment Videos
A trypsin-like platelet protease propagates protease-activated receptor-1 cleavage and platelet activation
F A Ofosu1, J Freedman, L Dewar
1Canadian Red Cross Society, Blood Services, Hamilton, Ontario, L8N 1H8 Canada and McMaster University, Department of Pathology, HSC 3N26, 1200 Main St. West, Hamilton, Ontario, L8N 3Z5 Canada. ofosuf@fhs.csu.mcmaster.ca
Abstract:
Protease-activated receptor-1 (PAR-1) is a G-protein-linked receptor on platelets and perivascular cells activated by alpha-thrombin and the PAR-1-activating peptide, SFLLRN. alpha-Thrombin activates PAR-1 by cleaving it at R41-S42 to release the 41-residue peptide TR(1-41). Unexpectedly, platelet activation with SFLLRN was also associated with PAR-1 cleavage and the release of TR(1-41). Both PAR-1 cleavage and platelet activation resulting from SFLLRN addition to platelets were markedly inhibited by the serine protease inhibitor 4, 2-(aminoethyl)-benzene sulphonylfluoride.HCl (pefabloc SC) and soybean trypsin inhibitor, but not by inhibitors of calpain, cysteine proteases or metalloproteases. Thus, a trypsin-like platelet protease propagates SFLLRN-dependent PAR-1 cleavage and platelet activation.