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dc.contributor.authorFurman, Mark I.
dc.contributor.authorNurden, Pauita
dc.contributor.authorBerndt, Michael C.
dc.contributor.authorNurden, Alan T.
dc.contributor.authorBenoit, Stephen E.
dc.contributor.authorBarnard, Marc R.
dc.contributor.authorOfosu, Frederick A.
dc.contributor.authorMichelson, Alan D.
dc.date2022-08-11T08:10:10.000
dc.date.accessioned2022-08-23T16:58:20Z
dc.date.available2022-08-23T16:58:20Z
dc.date.issued2000-11-01
dc.date.submitted2012-04-25
dc.identifier.citationThromb Haemost. 2000 Nov;84(5):897-903.
dc.identifier.issn0340-6245 (Linking)
dc.identifier.pmid11127874
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43344
dc.description.abstractThe 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.isoen_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.urlhttp://www.schattauer.de/en/magazine/subject-areas/journals-a-z/thrombosis-and-haemostasis/contents/archive/issue/891/manuscript/2599.html
dc.subjectAnimals
dc.subjectBlood Platelets
dc.subjectHumans
dc.subjectMice
dc.subjectPlatelet Glycoprotein GPIb-IX Complex
dc.subject*Platelet Membrane Glycoproteins
dc.subjectReceptors, Thrombin
dc.subjectSignal Transduction
dc.subjectThrombin
dc.subjectvon Willebrand Factor
dc.subjectHematology
dc.subjectOncology
dc.subjectPediatrics
dc.titleThe cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system
dc.typeJournal Article
dc.source.journaltitleThrombosis and haemostasis
dc.source.volume84
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/peds_hematology/22
dc.identifier.contextkey2796509
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.submissionpathpeds_hematology/22
dc.contributor.departmentDepartment of Pediatrics
dc.source.pages897-903


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