Linked Life Data

15967165

Source:http://linkedlifedata.com/resource/pubmed/id/15967165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-4
pubmed:dateCreated
2005-6-21
pubmed:abstractText
Endothelial cell (EC) migration has an important role in angiogenesis. Sphingosine-1 phosphate (S1P) stimulates EC migration via activation of Gi proteins. In this study, we characterized a mouse guanine nucleotide exchange factor (GEF) P-Rex2b for its regulation by Gbetagamma and PI3K and its role in S1P-induced Rac1 activation and cell migration in ECs. We found that co-expression of Gbetagamma or an active form of PI3K (PI3K(AC)) with P-Rex2b increased the SRE. Luciferase (SRE.L) reporter gene activity that can be stimulated by the Rho family of small GTPases including Rac1. Co-expression with P-Rex2b of Gbetagamma and PI3K(AC) or wild type PI3Kgamma that can be activated by Gbetagamma led to further increases in the reporter gene activity. Together with the finding that co-expression of Gbetagamma and/or PI3K(AC) increased the levels of active Rac1, we conclude that P-Rex2b is a Rac GEF that can be regulated by Gbetagamma and PI3K. Additionally, we demonstrated that Gbetagamma interacted with P-Rex2b, probably through P-Rex2b sequences at the PH domain and that the DEP and PDZ domains of P-Rex2b exerted an inhibitory effect on P-Rex2b's activity because their deletion increased the SER.L reporter gene activity. Furthermore, we found that P-Rex2b is involved in S1P-induced Rac1 activation and cell migration in ECs because siRNA-mediated suppression of P-Rex2b expression in ECs-diminished Rac1 activation and cell migration in response to S1P. Therefore, P-Rex2b is a physiologically significant Rac1 GEF that has an important role in the regulation of EC migration.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1098-8823
pubmed:author
pubmed:issnType
Print
pubmed:volume
76
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
95-104
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Role of guanine nucleotide exchange factor P-Rex-2b in sphingosine 1-phosphate-induced Rac1 activation and cell migration in endothelial cells.
pubmed:affiliation
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, 06030, USA. zli@neuron.uchu.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural