Linked Life Data

15054110

Source:http://linkedlifedata.com/resource/pubmed/id/15054110

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 10
pubmed:dateCreated
2004-4-19
pubmed:abstractText
Angiogenesis is critical for vascular remodeling during development and contributes to the pathogenesis of diseases such as cancer. Targeted disruption of several EphB class receptor tyrosine kinases results in vascular remodeling defects during embryogenesis. The role of EphA class receptors in vascular remodeling, however, is not well-characterized. We recently demonstrated that global inhibition of EphA receptors disrupts endothelial migration induced by ephrin, VEGF or tumor-derived signals, though the specific target remained undefined. Here, we report that EphA2 regulates endothelial cell assembly and migration through phosphoinositide (PI) 3-kinase-mediated activation of Rac1 GTPase in two model systems: primary bovine and murine pulmonary microvascular endothelial cells. EphA2-deficient endothelial cells fail to undergo vascular assembly and migration in response to ephrin-A1 in vitro. Ephrin-A1 stimulation induces PI3-kinase-dependent activation of Rac1 in wild-type endothelial cells, whereas EphA2-deficient cells fail to activate Rac1 upon stimulation. Expression of dominant negative PI3-kinase or Rac1 inhibits ephrin-A1-induced endothelial cell migration. Consistent with in vitro data, EphA2-deficient mice show a diminished angiogenic response to ephrin-A1 in vivo. Moreover, EphA2-deficient endothelial cells fail to assemble in vivo when transplanted into recipient mice. These data suggest that EphA2 is an essential regulator of post-natal angiogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2037-49
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15054110-Adenoviridae, pubmed-meshheading:15054110-Animals, pubmed-meshheading:15054110-Cattle, pubmed-meshheading:15054110-Cell Movement, pubmed-meshheading:15054110-Cell Proliferation, pubmed-meshheading:15054110-Cells, Cultured, pubmed-meshheading:15054110-Endothelium, Vascular, pubmed-meshheading:15054110-Enzyme Activation, pubmed-meshheading:15054110-Ephrin-A1, pubmed-meshheading:15054110-Ephrin-A2, pubmed-meshheading:15054110-Gene Expression Regulation, Enzymologic, pubmed-meshheading:15054110-Genes, Dominant, pubmed-meshheading:15054110-Guanosine Triphosphate, pubmed-meshheading:15054110-Immunoblotting, pubmed-meshheading:15054110-Immunoprecipitation, pubmed-meshheading:15054110-Lung, pubmed-meshheading:15054110-Mice, pubmed-meshheading:15054110-Microcirculation, pubmed-meshheading:15054110-Models, Genetic, pubmed-meshheading:15054110-Mutation, pubmed-meshheading:15054110-Neovascularization, Pathologic, pubmed-meshheading:15054110-Phosphatidylinositol 3-Kinases, pubmed-meshheading:15054110-Plasmids, pubmed-meshheading:15054110-Receptor, EphA2, pubmed-meshheading:15054110-Recombination, Genetic, pubmed-meshheading:15054110-rac1 GTP-Binding Protein
pubmed:year
2004
pubmed:articleTitle
EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation.
pubmed:affiliation
Division of Rhematology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't