Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
2004-9-6
pubmed:abstractText
Exposure of endothelial cells to vascular endothelial growth factor (VEGF) induced tyrosine phosphorylation of focal adhesion kinase (FAK) on site Tyr(407), an effect that required the association of VEGF receptor 2 (VEGFR2) with HSP90. The association of VEGFR2 with HSP90 involved the last 130 amino acids of VEGFR2 and was blocked by geldanamycin, a specific inhibitor of HSP90. Moreover, geldanamycin inhibited the VEGF-induced activation of the small GTPase RhoA, which resulted in an inhibition of phosphorylation of FAK on site Tyr(407). In this context, the inhibition of RhoA kinase (ROCK) with Y27632 or by expression of dominant negative forms of RhoA or ROCK impaired the VEGF-induced phosphorylation of Tyr(407) within FAK. In contrast to phosphorylation of Tyr(861), the phosphorylation of site Tyr(407) was insensitive to Src kinase inhibition by 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2). We also found that the recruitment of paxillin to FAK was inhibited by geldanamycin but not by PP2, whereas both geldanamycin and PP2 inhibited the recruitment of vinculin to FAK. In accordance, the recruitment of paxillin and vinculin to FAK was inhibited in cells that express the mutant FAK-Y407F, whereas the expression of the mutant Y861F inhibited the recruitment of paxillin but not of vinculin. Importantly, cell migration was abolished in cells in which the signal from the VEGFR2-HSP90 pathway was blocked by the expression of Delta130VEGFR2, a deletant of VEGFR2 that does not associate with HSP90. Our findings underscore for the first time the key role played by the VEGFR2-HSP90-RhoA-ROCK-FAK/Tyr(407) pathway in transducing the VEGF signal that leads to the assembly of focal adhesions and endothelial cell migration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Amides, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD18, http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones, http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine..., http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/HSP90 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic, http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PTK2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PXN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Paxillin, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/Quinones, http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine, http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor..., http://linkedlifedata.com/resource/pubmed/chemical/Vinculin, http://linkedlifedata.com/resource/pubmed/chemical/Y 27632, http://linkedlifedata.com/resource/pubmed/chemical/geldanamycin, http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein, http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39175-85
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15247219-Amides, pubmed-meshheading:15247219-Antigens, CD18, pubmed-meshheading:15247219-Benzoquinones, pubmed-meshheading:15247219-Cell Movement, pubmed-meshheading:15247219-Cells, Cultured, pubmed-meshheading:15247219-Cytoskeletal Proteins, pubmed-meshheading:15247219-DNA, Complementary, pubmed-meshheading:15247219-Endothelium, Vascular, pubmed-meshheading:15247219-Focal Adhesion Kinase 1, pubmed-meshheading:15247219-Focal Adhesion Protein-Tyrosine Kinases, pubmed-meshheading:15247219-Gene Expression Regulation, pubmed-meshheading:15247219-Gene Transfer Techniques, pubmed-meshheading:15247219-Genes, Dominant, pubmed-meshheading:15247219-Green Fluorescent Proteins, pubmed-meshheading:15247219-HSP90 Heat-Shock Proteins, pubmed-meshheading:15247219-Humans, pubmed-meshheading:15247219-Lactams, Macrocyclic, pubmed-meshheading:15247219-Luminescent Proteins, pubmed-meshheading:15247219-Mutation, pubmed-meshheading:15247219-Paxillin, pubmed-meshheading:15247219-Phosphoproteins, pubmed-meshheading:15247219-Phosphorylation, pubmed-meshheading:15247219-Precipitin Tests, pubmed-meshheading:15247219-Protein-Tyrosine Kinases, pubmed-meshheading:15247219-Pyridines, pubmed-meshheading:15247219-Quinones, pubmed-meshheading:15247219-Time Factors, pubmed-meshheading:15247219-Tyrosine, pubmed-meshheading:15247219-Umbilical Veins, pubmed-meshheading:15247219-Vascular Endothelial Growth Factor Receptor-2, pubmed-meshheading:15247219-Vinculin, pubmed-meshheading:15247219-rhoA GTP-Binding Protein, pubmed-meshheading:15247219-src-Family Kinases
pubmed:year
2004
pubmed:articleTitle
Regulation of vascular endothelial growth factor receptor 2-mediated phosphorylation of focal adhesion kinase by heat shock protein 90 and Src kinase activities.
pubmed:affiliation
Le Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, Québec G1R 2J6, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't