| http://purl.uniprot.org/citations/16990611 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16990611 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16990611 | http://www.w3.org/2000/01/rdf-schema#comment | "Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis, the major complication of atherosclerosis triggering myocardial infarction and stroke. A central regulatory pathway conveying inhibition of platelet activation/aggregation is nitric oxide (NO)/cyclic GMP (cGMP) signaling by cGMP-dependent protein kinase I (cGKI). However, the regulatory cascade downstream of cGKI mediating platelet inhibition is still unclear. Here, we show that the inositol-1,4,5-trisphosphate receptor-associated cGMP kinase substrate (IRAG) is abundantly expressed in platelets and assembled in a macrocomplex together with cGKIbeta and the inositol-1,4,5-trisphosphate receptor type I (InsP3RI). cGKI phosphorylates IRAG at Ser664 and Ser677 in intact platelets. Targeted deletion of the IRAG-InsP3RI interaction in IRAGDelta12/Delta12 mutant mice leads to a loss of NO/cGMP-dependent inhibition of fibrinogen-receptor activation and platelet aggregation. Intracellular calcium transients were not affected by DEA/NO or cGMP in mutant platelets. Furthermore, intravital microscopy shows that NO fails to prevent arterial thrombosis of the injured carotid artery in IRAGDelta12/Delta12 mutants. These findings reveal that interaction between IRAG and InsP3RI has a central role in NO/cGMP-dependent inhibition of platelet aggregation and in vivo thrombosis."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2005-10-026294"xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2005-10-026294"xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Wilm M."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Wilm M."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Werner M."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Werner M."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Hofmann F."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Hofmann F."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Kocher T."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Kocher T."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Massberg S."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Massberg S."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Schlossmann J."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Schlossmann J."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Antl M."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Antl M."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Eiglsperger C."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Eiglsperger C."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Konrad I."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "Konrad I."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "von Bruehl M.-L."xsd:string |
| http://purl.uniprot.org/citations/16990611 | http://purl.uniprot.org/core/author | "von Bruehl M.-L."xsd:string |