Linked Life Data

20697430

Source:http://linkedlifedata.com/resource/pubmed/id/20697430

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-12-2
pubmed:abstractText
Although VEGFR-3 deficiency disrupts blood vascular development during early embryogenesis, the underlying mechanism was not clear. To characterize its function in angiogenesis and lymphangiogenesis, we employed two genetically modified mouse models in this study, targeting the coding region for the ligand-binding domain (Vegfr3(?LBD)) or the tyrosine kinase domain with an inactivation point mutation (Vegfr3(TKmut)). We show that lymphatic growth was disrupted in Vegfr3(?LBD/?LBD) and Vegfr3(TKmut/TKmut) mice, but blood vessels developed normally in both embryo and yolk sac. Interestingly, in Vegfr3(?LBD/?LBD) but not Vegfr3(TKmut/TKmut) mice, lymph sac was present but there was lack of lymphangiogenic sprouting. We further demonstrate that both the wild-type and mutant forms of VEGFR-3 could form heterodimers with VEGFR-2, and decreased the level of phospho-VEGFR-2 and the downstream phospho-Erk1/2 in endothelial cells when they were treated with VEGF-A. These findings indicate that signaling mediated via VEGFR-3 activation by its cognate ligands (VEGF-C/-D) is not required for angiogenesis, and that VEGFR-3 may play a role in this process by modulating VEGFR-2-mediated signals.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1748-7838
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1319-31
pubmed:meshHeading
pubmed-meshheading:20697430-Animals, pubmed-meshheading:20697430-Dimerization, pubmed-meshheading:20697430-Embryo, Mammalian, pubmed-meshheading:20697430-Ligands, pubmed-meshheading:20697430-Lymphangiogenesis, pubmed-meshheading:20697430-Mice, pubmed-meshheading:20697430-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:20697430-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:20697430-Models, Animal, pubmed-meshheading:20697430-Point Mutation, pubmed-meshheading:20697430-Protein Structure, Tertiary, pubmed-meshheading:20697430-Signal Transduction, pubmed-meshheading:20697430-Vascular Endothelial Growth Factor A, pubmed-meshheading:20697430-Vascular Endothelial Growth Factor Receptor-2, pubmed-meshheading:20697430-Vascular Endothelial Growth Factor Receptor-3, pubmed-meshheading:20697430-Yolk Sac
pubmed:year
2010
pubmed:articleTitle
VEGFR-3 ligand-binding and kinase activity are required for lymphangiogenesis but not for angiogenesis.
pubmed:affiliation
Laboratory of Vascular and Cancer Biology, MOE Key Laboratory for Model Animal and Disease Study, Model Animal Research Institute, Nanjing University, 12 Xue Fu Road, Nanjing 210061, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't