Linked Life Data

18313900

Source:http://linkedlifedata.com/resource/pubmed/id/18313900

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-4-28
pubmed:abstractText
The immune modulator FTY720 is phosphorylated in vivo to FTY720 phosphate (FTY-P), which activates four sphingosine 1-phosphate (S1P) receptors including S1P(3). Upon activation with S1P, S1P(3) couples to G(i)- and G(q)-protein-dependent signalling pathways. Here we show that FTY-P selectively activates the S1P(3)-mediated and G(i)-coupled inhibition of adenylyl cyclase. Contemporaneously, it antagonizes the S1P-induced activation of G(q) via S1P(3) in intracellular calcium flux measurements, GTP-binding experiments, and flow cytometric analyses of activation-induced receptor down-regulation. In contrast to S1P, pre-treatment with FTY-P did not desensitize S1P-induced calcium flux or chemotaxis via S1P(3). The lack of receptor desensitization prevented S1P(3)-mediated migration to FTY-P. Human umbilical vein endothelial cells express S1P(1) and S1P(3), and respond to S1P and FTY-P by ERK1/2 phosphorylation and by intracellular calcium release in a pertussis toxin-sensitive manner. But whereas a mixture of S1P and FTY-P was not affecting ERK1/2 phosphorylation, the intracellular calcium flux was hampered with increasing amounts of FTY-P, which points to a cross-talk between S1P(1) and S1P(3). FTY-P is therefore one of the rare ligands which bind to a receptor that couples multiple G-proteins but selectively activates only one signalling pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0898-6568
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1125-33
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Selective activation of G alpha i mediated signalling of S1P3 by FTY720-phosphate.
pubmed:affiliation
Institute for Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hanover, Germany. sensken.sven-christian@mh-hannover.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't