Source:http://linkedlifedata.com/resource/pubmed/id/15122338
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
28
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| pubmed:dateCreated |
2004-6-17
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| pubmed:abstractText |
Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis by stimulating migration, proliferation and organization of endothelium, through the activation of signaling pathways involving Src tyrosine kinase. As we had previously shown that Src-mediated activation of diacylglycerol kinase-alpha (Dgk-alpha) is required for hepatocytes growth factor-stimulated cell migration, we asked whether Dgk-alpha is involved in the transduction of angiogenic signaling. In PAE-KDR cells, an endothelial-derived cell line expressing VEGFR-2, VEGF-A165, stimulates the enzymatic activity of Dgk-alpha: activation is inhibited by R59949, an isoform-specific Dgk inhibitor, and is dependent on Src tyrosine kinase, with which Dgk-alpha forms a complex. Conversely in HUVEC, VEGF-A165-induced activation of Dgk is only partially sensitive to R59949, suggesting that also other isoforms may be activated, albeit still dependent on Src tyrosine kinase. Specific inhibition of Dgk-alpha, obtained in both cells by R59949 and in PAE-KDR by expression of Dgk-alpha dominant-negative mutant, impairs VEGF-A165-dependent chemotaxis, proliferation and in vitro angiogenesis. In addition, in HUVEC, specific downregulation of Dgk-alpha by siRNA impairs in vitro angiogenesis on matrigel, further suggesting the requirement for Dgk-alpha in angiogenic signaling in HUVEC. Thus, we propose that activation of Dgk-alpha generates a signal essential for both proliferative and migratory response to VEGF-A165, suggesting that it may constitute a novel pharmacological target for angiogenesis control.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Diacylglycerol Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0950-9232
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2004 Nature Publishing Group
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| pubmed:issnType |
Print
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| pubmed:day |
17
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| pubmed:volume |
23
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4828-38
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15122338-Animals,
pubmed-meshheading:15122338-Aorta,
pubmed-meshheading:15122338-Cell Division,
pubmed-meshheading:15122338-Cells, Cultured,
pubmed-meshheading:15122338-Chemotaxis,
pubmed-meshheading:15122338-Diacylglycerol Kinase,
pubmed-meshheading:15122338-Endothelium, Vascular,
pubmed-meshheading:15122338-Enzyme Activation,
pubmed-meshheading:15122338-Genetic Vectors,
pubmed-meshheading:15122338-Humans,
pubmed-meshheading:15122338-Neovascularization, Physiologic,
pubmed-meshheading:15122338-RNA, Small Interfering,
pubmed-meshheading:15122338-RNA Interference,
pubmed-meshheading:15122338-Recombinant Proteins,
pubmed-meshheading:15122338-Retroviridae,
pubmed-meshheading:15122338-Swine,
pubmed-meshheading:15122338-Transfection,
pubmed-meshheading:15122338-Vascular Endothelial Growth Factor A
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| pubmed:year |
2004
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| pubmed:articleTitle |
Activation of diacylglycerol kinase alpha is required for VEGF-induced angiogenic signaling in vitro.
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| pubmed:affiliation |
Department of Medical Sciences, University Amedeo Avogadro of Piemonte Orientale, v. Solaroli 17, 28100, Novara, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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