Linked Life Data

11069896

Source:http://linkedlifedata.com/resource/pubmed/id/11069896

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-2-22
pubmed:abstractText
The previously cloned rat nerve growth factor-regulated G protein-coupled receptor NRG-1 (Glickman, M., Malek, R. L., Kwitek-Black, A. E., Jacob, H. J., and Lee N. H. (1999) Mol. Cell. Neurosci. 14, 141-52), also known as EDG-8, binds sphingosine-1-phosphate (S1P) with high affinity and specificity. In this paper we examined the signal transduction pathways regulated by the binding of S1P to EDG-8. In Chinese hamster ovary cells heterologously expressing EDG-8, S1P inhibited forskolin-induced cAMP accumulation and activated c-Jun NH2-terminal kinase. Surprisingly, S1P inhibited serum-induced activation of extracellular regulated protein kinase 1 and 2 (ERK1/2). Treatment with pertussis toxin, which ADP-ribosylates and inactivates G(i), blocked S1P-mediated inhibition of cAMP accumulation, but had no effect on c-Jun NH2-terminal kinase activation or inhibition of ERK1/2. The inhibitory effect of S1P on ERK1/2 activity was abolished by treatment with orthovanadate, suggesting the involvement of a tyrosine phosphatase. A subunit selective [35S] guanosine 5'-3-O-(thio)triphosphate binding assay demonstrates that EDG-8 activated G(i/o) and G12 but not Gs and G(q/11) in response to S1P. In agreement, EDG-8 did not stimulate phosphoinositide turnover or cAMP accumulation. The ability of S1P to induce mitogenesis in cells expressing the EDG-1 subfamily of G protein-coupled receptors is well characterized. In contrast, S1P inhibited proliferation in Chinese hamster ovary cells expressing EDG-8 but not empty vector. The antiproliferative effect, like S1P-mediated ERK1/2 inhibition, was orthovanadate-sensitive and pertussis toxin-insensitive. Our results indicate that EDG-8, a member of the EDG-1 subfamily, couples to unique signaling pathways.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids, http://linkedlifedata.com/resource/pubmed/chemical/Neuregulin-1, http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lysophospholipid, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine, http://linkedlifedata.com/resource/pubmed/chemical/Vanadates, http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella, http://linkedlifedata.com/resource/pubmed/chemical/sphingosine 1-phosphate
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5692-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Nrg-1 belongs to the endothelial differentiation gene family of G protein-coupled sphingosine-1-phosphate receptors.
pubmed:affiliation
Department of Molecular and Cellular Biology, Institute for Genomic Research, Rockville, Maryland 20850, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't