Source:http://linkedlifedata.com/resource/pubmed/id/19477952
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2009-8-28
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pubmed:abstractText |
On vascular endothelial growth factor (VEGF) stimulation, both VEGF R1 and R2 receptors were phosphorylated in ovine fetoplacental artery endothelial (oFPAE) cells. Treatment with VEGF stimulated both time- and dose-dependent activation of ERK2/1 in oFPAE cells. VEGF-induced ERK2/1 activation was mediated by VEGFR2, but not VEGFR1, and was linked to intracellular calcium, protein kinase C, and Raf-1. VEGF stimulated oFPAE cell proliferation, migration, and tube formation in vitro. Blockade of ERK2/1 pathway attenuated VEGF-induced cell proliferation and tube formation but failed to inhibit migration in oFPAE cells. Disruption of caveolae by cholesterol depletion with methyl-beta-cyclodextrin or by down-regulation of its structural protein caveolin-1 blunted VEGF-induced ERK2/1 activation, proliferation, and tube formation in oFPAE cells, indicating an essential role of integral caveolae in these VEGF-induced responses. Adenoviral overexpression of caveolin-1 and addition of a caveolin scaffolding domain peptide also inhibited VEGF-stimulated ERK2/1 activation, cell proliferation, and tube formation in oFPAE cells. Furthermore, molecules comprising the ERK2/1 signaling module, including VEGFR2, protein kinase Calpha, Raf-1, MAPK kinase 1/2, and ERK2/1, resided with caveolin-1 in caveolae. VEGF transiently stimulated ERK2/1 activation in the caveolae similarly as in intact cells. Caveolae disruption greatly diminished ERK2/1 activation by VEGF in oFPAE cell caveolae. We conclude that caveolae function as a platform for compartmentalizing the VEGF-induced ERK2/1 signaling module. Caveolin-1 and caveolae play a paradoxical role in regulating VEGF-induced ERK2/1 activation and in vitro angiogenesis as evidenced by the similar inhibitory effects of down-regulation and overexpression of caveolin-1 and disruption of caveolae in oFPAE cells.
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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/Caveolin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1944-9917
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pubmed:author | |
pubmed:issnType |
Electronic
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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 |
1428-44
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pubmed:dateRevised |
2010-9-2
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pubmed:meshHeading |
pubmed-meshheading:19477952-Animals,
pubmed-meshheading:19477952-Arteries,
pubmed-meshheading:19477952-Caveolin 1,
pubmed-meshheading:19477952-Endothelial Cells,
pubmed-meshheading:19477952-Female,
pubmed-meshheading:19477952-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:19477952-Humans,
pubmed-meshheading:19477952-Mice,
pubmed-meshheading:19477952-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:19477952-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:19477952-Models, Biological,
pubmed-meshheading:19477952-Neovascularization, Pathologic,
pubmed-meshheading:19477952-Placenta,
pubmed-meshheading:19477952-Polymerase Chain Reaction,
pubmed-meshheading:19477952-Vascular Endothelial Growth Factor A
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pubmed:year |
2009
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pubmed:articleTitle |
Compartmentalizing VEGF-induced ERK2/1 signaling in placental artery endothelial cell caveolae: a paradoxical role of caveolin-1 in placental angiogenesis in vitro.
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pubmed:affiliation |
Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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