Source:http://linkedlifedata.com/resource/pubmed/id/15175347
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
34
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| pubmed:dateCreated |
2004-8-16
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| pubmed:abstractText |
UTP stimulates the expression of pro-inflammatory vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells through activation of the P2Y(2) nucleotide receptor P2Y(2)R. Here, we demonstrated that activation of the P2Y(2)R induced rapid tyrosine phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2 in human coronary artery endothelial cells (HCAEC). RNA interference targeting VEGFR-2 or inhibition of VEGFR-2 tyrosine kinase activity abolishes P2Y(2)R-mediated VCAM-1 expression. Furthermore, VEGFR-2 and the P2Y(2)R co-localize upon UTP stimulation. Deletion or mutation of two Src homology-3-binding sites in the C-terminal tail of the P2Y(2)R or inhibition of Src kinase activity abolished the P2Y(2)R-mediated transactivation of VEGFR-2 and subsequently inhibited UTP-induced VCAM-1 expression. Moreover, activation of VEGFR-2 by UTP leads to the phosphorylation of Vav2, a guanine nucleotide exchange factor for Rho family GTPases. Using a binding assay to measure the activity of the small GTPases Rho, we found that stimulation of HCAEC by UTP increased the activity of RhoA and Rac1 (but not Cdc42). Significantly, a dominant negative form of RhoA inhibited P2Y(2)R-mediated VCAM-1 expression, whereas expression of dominant negative forms of Cdc42 and Rac1 had no effect. These data indicate a novel mechanism whereby a nucleotide receptor transactivates a receptor tyrosine kinase to generate an inflammatory response associated with atherosclerosis.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/P2RY2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2Y2,
http://linkedlifedata.com/resource/pubmed/chemical/Uridine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
20
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| pubmed:volume |
279
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
35679-86
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:15175347-Amino Acid Sequence,
pubmed-meshheading:15175347-Animals,
pubmed-meshheading:15175347-Arteriosclerosis,
pubmed-meshheading:15175347-Binding Sites,
pubmed-meshheading:15175347-Cell Line,
pubmed-meshheading:15175347-Coronary Vessels,
pubmed-meshheading:15175347-Endothelium, Vascular,
pubmed-meshheading:15175347-Humans,
pubmed-meshheading:15175347-Molecular Sequence Data,
pubmed-meshheading:15175347-Phosphorylation,
pubmed-meshheading:15175347-Rabbits,
pubmed-meshheading:15175347-Receptors, Purinergic P2,
pubmed-meshheading:15175347-Receptors, Purinergic P2Y2,
pubmed-meshheading:15175347-Signal Transduction,
pubmed-meshheading:15175347-Structure-Activity Relationship,
pubmed-meshheading:15175347-Uridine Triphosphate,
pubmed-meshheading:15175347-Vascular Cell Adhesion Molecule-1,
pubmed-meshheading:15175347-Vascular Endothelial Growth Factor Receptor-2
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| pubmed:year |
2004
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| pubmed:articleTitle |
The P2Y2 nucleotide receptor mediates vascular cell adhesion molecule-1 expression through interaction with VEGF receptor-2 (KDR/Flk-1).
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| pubmed:affiliation |
Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65212, USA. seyec@missouri.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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