| http://purl.uniprot.org/citations/19700402 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19700402 | http://www.w3.org/2000/01/rdf-schema#comment | "Glycoprotein (GP) VI is a critical platelet collagen receptor. Phosphoinositide 3-kinase (PI3K) plays an important role in GPVI-mediated platelet activation, yet the major PI3K isoforms involved in this process have not been identified. In addition, stimulation of GPVI results in the activation of Akt, a downstream effector of PI3K. Thus, we investigated the contribution of PI3K isoforms to GPVI-mediated platelet activation and Akt activation. A protein kinase C inhibitor GF 109203X or a P2Y(12) receptor antagonist AR-C69931MX partly reduced GPVI-induced Akt phosphorylation. Platelets from mice dosed with clopidogrel also showed partial Akt phosphorylation, indicating that GPVI-mediated Akt phosphorylation is regulated by both secretion-dependent and -independent pathways. In addition, GPVI-induced Akt phosphorylation in the presence of ADP antagonists was completely inhibited by PI3K inhibitor LY294002 and PI3Kbeta inhibitor TGX-221 indicating an essential role of PI3Kbeta in Akt activation directly downstream of GPVI. Moreover, GPVI-mediated platelet aggregation, secretion, and intracellular Ca(2+) mobilization were significantly inhibited by TGX-221, and less strongly inhibited by PI3Kalpha inhibitor PIK75, but were not affected by PI3Kgamma inhibitor AS252424 and PI3Kdelta inhibitor IC87114. Consistently, GPVI-induced integrin alpha(IIb)beta(3) activation of PI3Kgamma(-/-) and PI3Kdelta(-/-) platelets also showed no significant difference compared with wild-type platelets. These results demonstrate that GPVI-induced Akt activation in platelets is dependent in part on G(i) stimulation through P2Y(12) receptor activation by secreted ADP. In addition, a significant portion of GPVI-dependent, ADP-independent Akt activation also exists, and PI3Kbeta plays an essential role in GPVI-mediated platelet aggregation and Akt activation."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m109.048553"xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/author | "Jackson S.P."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/author | "Kim S."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/author | "Kunapuli S.P."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/author | "Daniel J.L."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/author | "Mangin P."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/author | "Dangelmaier C."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/author | "Lillian R."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/pages | "33763-33772"xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/title | "Role of phosphoinositide 3-kinase beta in glycoprotein VI-mediated Akt activation in platelets."xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://purl.uniprot.org/core/volume | "284"xsd:string |
| http://purl.uniprot.org/citations/19700402 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19700402 |
| http://purl.uniprot.org/citations/19700402 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19700402 |
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| http://purl.uniprot.org/uniprot/#_A0A142IKA9-mappedCitation-19700402 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19700402 |
| http://purl.uniprot.org/uniprot/#_B2RR15-mappedCitation-19700402 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19700402 |
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| http://purl.uniprot.org/uniprot/#_B4DZI3-mappedCitation-19700402 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19700402 |
| http://purl.uniprot.org/uniprot/#_B0LPE5-mappedCitation-19700402 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/19700402 |