A trypsin-like platelet protease propagates protease-activated receptor-1 cleavage and platelet activation.
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.
Ofosu
F A
FA
Canadian 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
Freedman
J
J
Dewar
L
L
Song
Y
Y
Fenton
J W
JW
D003094:Collagen / Q000494:pharmacology; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000187:drug effects / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology
D010446:Peptide Fragments; D011480:Protease Inhibitors; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013450:Sulfones; D014361:Trypsin Inhibitors; C082835:thrombin receptor peptide (42-47); C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D003094:Collagen; D012697:Serine Endopeptidases; D014357:Trypsin; D013917:Thrombin