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http://purl.uniprot.org/citations/22075250http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22075250http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The goal of this study was to investigate the potential crosstalk between Rap1 and Rac1, 2 small GTPases central to platelet activation, particularly downstream of the collagen receptor GPVI.

Methods and results

We compared the activation response of platelets with impaired Rap signaling (double knock-out; deficient in both the guanine nucleotide exchange factor, CalDAG-GEFI, and the Gi-coupled receptor for ADP, P2Y12), to that of wild-type platelets treated with a small-molecule Rac inhibitor, EHT 1864 (wild-type /EHT). We found that Rac1 is sequentially activated downstream of Rap1 on stimulation via GPVI. In return, Rac1 provides important feedback for both CalDAG-GEFI- and P2Y12-dependent activation of Rap1. When analyzing platelet responses controlled by Rac1, we observed (1) impaired lamellipodia formation, clot retraction, and granule release in both double knock-out and EHT 1864-treated wild-type platelets; and (2) reduced calcium store release in EHT 1864-treated wild-type but not double knock-out platelets. Consistent with the latter finding, we identified 2 pools of Rac1, one activated immediately downstream of GPVI and 1 activated downstream of Rap1.

Conclusions

We demonstrate important crosstalk between Rap1 and Rac1 downstream of GPVI. Whereas Rap1 signaling directly controls sustained Rac1 activation, Rac1 affects CalDAG-GEFI- and P2Y12-dependent Rap1 activation via its role in calcium mobilization and granule/ADP release, respectively."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.111.239194"xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Bergmeier W."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Conley P.B."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Holinstat M."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Andre P."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Leblond B."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Stefanini L."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Boulaftali Y."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Desire L."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/author"Ouellette T.D."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/pages"434-441"xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/title"Rap1-Rac1 circuits potentiate platelet activation."xsd:string
http://purl.uniprot.org/citations/22075250http://purl.uniprot.org/core/volume"32"xsd:string
http://purl.uniprot.org/citations/22075250http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22075250
http://purl.uniprot.org/citations/22075250http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22075250
http://purl.uniprot.org/uniprot/#_A0A0G2JGU7-mappedCitation-22075250http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22075250
http://purl.uniprot.org/uniprot/#_D3Z2F9-mappedCitation-22075250http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22075250
http://purl.uniprot.org/uniprot/#_D3YXD6-mappedCitation-22075250http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22075250
http://purl.uniprot.org/uniprot/#_D3Z3N3-mappedCitation-22075250http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22075250
http://purl.uniprot.org/uniprot/#_D6RDD3-mappedCitation-22075250http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22075250
http://purl.uniprot.org/uniprot/#_D3YZP1-mappedCitation-22075250http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22075250
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