Linked Life Data

19233262

Source:http://linkedlifedata.com/resource/pubmed/id/19233262

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-3-30
pubmed:abstractText
Gab1 was previously described as a positive modulator of Akt, Src, ERK1/2, endothelial cell migration, and capillary formation in response to vascular endothelial growth factor (VEGF). However, its involvement in endothelial cell survival, as well as the potential contribution of the other family member Gab2 to signalling and biological responses remained unknown. Here, we show that Gab2 is tyrosine phosphorylated in a Grb2-dependent manner downstream of activated VEGF receptor-2 (VEGFR2), and that it associates with signalling proteins including PI3K and SHP2, but apparently not with the receptor. Similarly to Gab1, over-expression of Gab2 induces endothelial cell migration in response to VEGF, whereas its depletion using siRNAs results in its reduction. Importantly, depletion of both Gab1 and Gab2 leads to an even greater inhibition of VEGF-induced cell migration. However, contrary to what has been reported for Gab1, the silencing of Gab2 results in increased Src, Akt and ERK1/2 activation, slightly reduced p38 phosphorylation, and up-regulation of Gab1 protein levels. Accordingly, re-expression of Gab2 in Gab2-/- fibroblasts leads to opposite results, suggesting that the modulation of both Gab2 and Gab1 expression in these conditions might contribute to the impaired signalling observed. Consistent with their opposite roles on Akt, the depletion of Gab1, but not of Gab2, results in reduced FOXO1 phosphorylation and VEGF-mediated endothelial cell survival. Mutation of VEGFR2 Y801 and Y1214, which abrogates the phosphorylation of Gab1, also correlates with inhibition of Akt. Altogether, these results underscore the non-redundant and essential roles of Gab1 and Gab2 in endothelial cells, and suggest major contributions of these proteins during in vivo angiogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1873-3913
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
943-53
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19233262-Adaptor Proteins, Signal Transducing, pubmed-meshheading:19233262-Animals, pubmed-meshheading:19233262-Cattle, pubmed-meshheading:19233262-Cell Line, pubmed-meshheading:19233262-Cell Movement, pubmed-meshheading:19233262-Cell Survival, pubmed-meshheading:19233262-Endothelial Cells, pubmed-meshheading:19233262-Enzyme Activation, pubmed-meshheading:19233262-Humans, pubmed-meshheading:19233262-Mice, pubmed-meshheading:19233262-Mutant Proteins, pubmed-meshheading:19233262-Phosphoproteins, pubmed-meshheading:19233262-Phosphorylation, pubmed-meshheading:19233262-Protein Binding, pubmed-meshheading:19233262-Proto-Oncogene Proteins c-akt, pubmed-meshheading:19233262-Signal Transduction, pubmed-meshheading:19233262-Vascular Endothelial Growth Factor A, pubmed-meshheading:19233262-Vascular Endothelial Growth Factor Receptor-2
pubmed:year
2009
pubmed:articleTitle
Non-redundant roles of the Gab1 and Gab2 scaffolding adapters in VEGF-mediated signalling, migration, and survival of endothelial cells.
pubmed:affiliation
Centre de recherche du Centre Hospitalier de l'Université de Montréal, 1560 rue Sherbrooke est, Montréal, Québec, Canada. christine.caron@umontreal.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't