title: Tethered ligand-derived peptides of proteinase-activated receptor 3 (PAR3) activate PAR1 and PAR2 in Jurkat T cells.
abstract: Proteinase-activated receptors (PARs) can activate a number of signalling events, including T-cell signal-transduction pathways. Recent data suggest that the activation of PARs 1, 2 and 3 in Jurkat T-leukaemic cells induces tyrosine phosphorylation of the haematopoietic signal transducer protein, VAV1. To activate the PARs, this study used the agonist peptides SFLLRNPNDK, SLIGKVDGTS and TFRGAPPNSF, which are based on the sequences of the tethered ligand sequences of human PARs 1, 2 and 3, respectively. Here, we show that peptides based on either the human or murine PAR(3)-derived tethered ligand sequences (TFRGAP-NH(2) or SFNGGP-NH(2)) do not activate PAR(3), but rather activate PARs 1 and 2, either in Jurkat or in other PAR-expressing cells. Furthermore, whilst thrombin activates only Jurkat PAR(1), trypsin activates both PARs 1 and 2 and also disarms Jurkat PAR(1) for thrombin activation. We conclude therefore that in Jurkat or related T cells, signalling via PARs that can affect VAV1 phosphorylation is mediated via PAR 1 or 2, or both, and that distinct serine proteinases may potentially differentially affect T-cell function in the settings of inflammation.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada. khansen@ucalgary.ca
authors.forename: Kristina K
authors.initials: KK
authors.lastname: Hansen
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Saifeddine
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D044463:Receptor, PAR-1 / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D018179:Receptors, Thrombin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014357:Trypsin / Q000494:pharmacology
chemical_list: D008024:Ligands; D010446:Peptide Fragments; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; D014357:Trypsin