| http://purl.uniprot.org/citations/21391917 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21391917 | http://www.w3.org/2000/01/rdf-schema#comment | "PARs (protease-activated receptors) 1 and 4 belong to the family of G-protein-coupled receptors which induce both G(α12/13) and G(αq) signalling. By applying the specific PAR1- and PAR4-activating hexapeptides, SFLLRN and AYPGKF respectively, we found that aggregation of isolated human platelets mediated via PAR1, but not via PAR4, is abolished upon homologous receptor activation in a concentration- and time-dependent fashion. This effect was not due to receptor internalization, but to a decrease in Ca²⁺ mobilization, PKC (protein kinase C) signalling and α-granule secretion, as well as to a complete lack of dense granule secretion. Interestingly, subthreshold PAR4 activation rapidly abrogated PAR1 signalling desensitization by differentially reconstituting these affected signalling events and functional responses, which was sufficient to re-establish aggregation. The lack of ADP release and P2Y₁₂ receptor-induced G(αi) signalling accounted for the loss of the aggregation response, as mimicking G(αi/z) signalling with 2-MeS-ADP (2-methylthioadenosine-5'-O-diphosphate) or epinephrine (adrenaline) could substitute for intermediate PAR4 activation. Finally, we found that the re-sensitization of PAR1 signalling-induced aggregation via PAR4 relied on PKC-mediated release of both ADP from dense granules and fibrinogen from α-granules. The present study elucidates further differences in human platelet PAR signalling regulation and provides evidence for a cross-talk in which PAR4 signalling counteracts mechanisms involved in PAR1 signalling down-regulation."xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.org/dc/terms/identifier | "doi:10.1042/bj20101360"xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/author | "Nylander M."xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/author | "Haglund L."xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/author | "Lindahl T.L."xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/author | "Falker K."xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/author | "Grenegard M."xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/author | "Gunnarsson P."xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/name | "Biochem J"xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/pages | "469-480"xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/title | "Protease-activated receptor 1 (PAR1) signalling desensitization is counteracted via PAR4 signalling in human platelets."xsd:string |
| http://purl.uniprot.org/citations/21391917 | http://purl.uniprot.org/core/volume | "436"xsd:string |
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