The cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system
dc.contributor.author | Furman, Mark I. | |
dc.contributor.author | Nurden, Pauita | |
dc.contributor.author | Berndt, Michael C. | |
dc.contributor.author | Nurden, Alan T. | |
dc.contributor.author | Benoit, Stephen E. | |
dc.contributor.author | Barnard, Marc R. | |
dc.contributor.author | Ofosu, Frederick A. | |
dc.contributor.author | Michelson, Alan D. | |
dc.date | 2022-08-11T08:10:10.000 | |
dc.date.accessioned | 2022-08-23T16:58:20Z | |
dc.date.available | 2022-08-23T16:58:20Z | |
dc.date.issued | 2000-11-01 | |
dc.date.submitted | 2012-04-25 | |
dc.identifier.citation | Thromb Haemost. 2000 Nov;84(5):897-903. | |
dc.identifier.issn | 0340-6245 (Linking) | |
dc.identifier.pmid | 11127874 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/43344 | |
dc.description.abstract | The only known function of the 41 amino acid cleaved peptide (TR1-41) of the seven transmembrane domain thrombin receptor (PARI) is to activate platelets (as determined by aggregation, surface P-selectin, and fibrinogen binding to activated GPIIb-IIIa). We now demonstrate that TR1-41 results in a concentration-dependent decrease in the platelet surface expression of each component of the GPIb-IX-V complex, as determined by flow cytometry with a panel of monoclonal antibodies (including 6D1, directed against the von Willebrand factor binding site on GPIbalpha, and TM60, directed against the thrombin binding site on GPIbalpha). TR1-41 also decreased ristocetin-induced platelet agglutination. Immunoblotting after incubation of platelets with TR1-41 revealed neither a loss of platelet GPIb nor increase in supernatant GPIb fragments. As demonstrated by immunoelectron microscopy, TR1-41 resulted in a redistribution of GPIb, GPIX, and GPV from the platelet surface to the surface-connected canalicular system (SCCS). In summary, the cleaved peptide (TR1-41) of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the SCCS, thereby negatively regulating the GPIbalpha binding sites for von Willebrand factor and thrombin. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11127874&dopt=Abstract">Link to article in PubMed</a> | |
dc.relation.url | http://www.schattauer.de/en/magazine/subject-areas/journals-a-z/thrombosis-and-haemostasis/contents/archive/issue/891/manuscript/2599.html | |
dc.subject | Animals | |
dc.subject | Blood Platelets | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Platelet Glycoprotein GPIb-IX Complex | |
dc.subject | *Platelet Membrane Glycoproteins | |
dc.subject | Receptors, Thrombin | |
dc.subject | Signal Transduction | |
dc.subject | Thrombin | |
dc.subject | von Willebrand Factor | |
dc.subject | Hematology | |
dc.subject | Oncology | |
dc.subject | Pediatrics | |
dc.title | The cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system | |
dc.type | Journal Article | |
dc.source.journaltitle | Thrombosis and haemostasis | |
dc.source.volume | 84 | |
dc.source.issue | 5 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/peds_hematology/22 | |
dc.identifier.contextkey | 2796509 | |
html.description.abstract | <p>The only known function of the 41 amino acid cleaved peptide (TR1-41) of the seven transmembrane domain thrombin receptor (PARI) is to activate platelets (as determined by aggregation, surface P-selectin, and fibrinogen binding to activated GPIIb-IIIa). We now demonstrate that TR1-41 results in a concentration-dependent decrease in the platelet surface expression of each component of the GPIb-IX-V complex, as determined by flow cytometry with a panel of monoclonal antibodies (including 6D1, directed against the von Willebrand factor binding site on GPIbalpha, and TM60, directed against the thrombin binding site on GPIbalpha). TR1-41 also decreased ristocetin-induced platelet agglutination. Immunoblotting after incubation of platelets with TR1-41 revealed neither a loss of platelet GPIb nor increase in supernatant GPIb fragments. As demonstrated by immunoelectron microscopy, TR1-41 resulted in a redistribution of GPIb, GPIX, and GPV from the platelet surface to the surface-connected canalicular system (SCCS). In summary, the cleaved peptide (TR1-41) of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the SCCS, thereby negatively regulating the GPIbalpha binding sites for von Willebrand factor and thrombin.</p> | |
dc.identifier.submissionpath | peds_hematology/22 | |
dc.contributor.department | Department of Pediatrics | |
dc.source.pages | 897-903 |