Linked Life Data

20179099

Source:http://linkedlifedata.com/resource/pubmed/id/20179099

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-2-24
pubmed:abstractText
Mammalian Ras, which is encoded by three independent genes, has been thought to be a versatile component of intracellular signalling. However, when, where and how Ras signalling plays essential roles in development and whether the three Ras genes have overlapping functions in particular cells remain unclear. Here, we show that the three Ras proteins dose-dependently regulate lymphatic vessel growth in mice. We find that lymphatic vessel hypoplasia is a common phenotype in Ras compound knockout mice and that overexpressed normal Ras in an endothelial cell lineage selectively causes lymphatic vessel hyperplasia in vivo. Overexpression of normal Ras in lymphatic endothelial cells leads to sustained MAPK activation, cellular viability and enhanced endothelial network formation under serum-depleted culture conditions in vitro, and knockdown of endogenous Ras in lymphatic endothelial cells impairs cell proliferation, MAPK activation, cell migration and endothelial network formation. Ras overexpression and knockdown result in up- and downregulation of vascular endothelial growth factor receptor (VEGFR) 3 expression, respectively, in lymphatic endothelial cells in vitro. The close link between Ras and VEGFR3 in vitro is consistent with the result that Ras knockout and transgenic alleles are genetic modifiers in lymphatic vessel hypoplasia caused by Vegfr3 haploinsufficiency. Our findings demonstrate a cooperative function of the three Ras proteins in normal development, and also provide a novel aspect of VEGFR3 signalling modulated by Ras in lymphangiogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1477-9129
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
137
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1003-13
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
H-, N- and Kras cooperatively regulate lymphatic vessel growth by modulating VEGFR3 expression in lymphatic endothelial cells in mice.
pubmed:affiliation
Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't