Source:http://linkedlifedata.com/resource/pubmed/id/17382929
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
2007-4-23
|
| pubmed:abstractText |
Vascular endothelial growth factor (VEGF) receptor activation regulates endothelial cell (EC) survival, migration and proliferation. Recently, it was suggested the cross-talk between the VEGF receptors-1 (FLT-1) and -2 (KDR) modulated several of these functions, but the detailed molecular basis for such interactions remained unexplained. Here we demonstrate for the first time that VEGF stimulation of EC monolayers induced a rapid FLT-1-mediated internalization of KDR to the nucleus, via microtubules and the endocytic pathway, internalization which required the activation of PI 3-kinase/AKT. KDR deletion mutants were generated in several tyrosine residues; in these, VEGF-induced KDR internalization was impaired, demonstrating this process required activation (phosphorylation) of the receptor. Furthermore, we demonstrate that in vitro wounding of EC monolayers leads to a rapid and transient internalization of VEGF+KDR to the nucleus, which is essential for monolayer recovery. Notably, FLT-1 blockade impedes VEGF and KDR activation and internalization, blocking endothelial monolayer recovery. Our data reveal a previously unrecognized mechanism induced by VEGF on EC, which regulates EC recovery following wounding, and as such indicate novel targets for therapeutic intervention.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0014-4827
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
313
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1561-74
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:17382929-Animals,
pubmed-meshheading:17382929-Cell Nucleus,
pubmed-meshheading:17382929-Cells, Cultured,
pubmed-meshheading:17382929-Endocytosis,
pubmed-meshheading:17382929-Endothelial Cells,
pubmed-meshheading:17382929-Endothelium, Vascular,
pubmed-meshheading:17382929-Humans,
pubmed-meshheading:17382929-Mice,
pubmed-meshheading:17382929-Microtubules,
pubmed-meshheading:17382929-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17382929-Protein Transport,
pubmed-meshheading:17382929-Receptor Cross-Talk,
pubmed-meshheading:17382929-Signal Transduction,
pubmed-meshheading:17382929-Umbilical Veins,
pubmed-meshheading:17382929-Vascular Endothelial Growth Factor A,
pubmed-meshheading:17382929-Vascular Endothelial Growth Factor Receptor-1,
pubmed-meshheading:17382929-Vascular Endothelial Growth Factor Receptor-2,
pubmed-meshheading:17382929-Wound Healing
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| pubmed:year |
2007
|
| pubmed:articleTitle |
VEGF and VEGFR-2 (KDR) internalization is required for endothelial recovery during wound healing.
|
| pubmed:affiliation |
Angiogenesis Laboratory, Centro de Investigação em Patobiologia Molecular, Instituto Português de Oncologia Francisco Gentil-CROL, SA, Lisboa, Portugal.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|