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rdf:type |
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lifeskim:mentions |
umls-concept:C0031621,
umls-concept:C0035820,
umls-concept:C0074992,
umls-concept:C0458827,
umls-concept:C0752312,
umls-concept:C1267092,
umls-concept:C1332794,
umls-concept:C1414253,
umls-concept:C1424650,
umls-concept:C1539079,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1948023
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pubmed:dateCreated |
1999-5-4
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pubmed:abstractText |
We report here that cultured airway smooth muscle cells contain transcripts of endothelial differentiation gene 1 (EDG-1), a prototypical orphan Gi-coupled receptor whose natural ligand is sphingosine 1-phosphate (S1P). This is consistent with data that showed that S1P activated both c-Src and p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) in a pertussis toxin (PTX)-sensitive manner in these cells. An essential role for c-Src was confirmed by using the c-Src inhibitor, PP1, which markedly decreased p42/p44 MAPK activation. We have also shown that phosphoinositide 3-kinase (PI-3K) inhibitors (wortmannin and LY294002) decreased p42/p44 MAPK activation. An essential role for PI-3K was supported by experiments that showed that PI-3K activity was increased in Grb-2 immunoprecipitates from S1P-stimulated cells. Significantly, Grb-2 associated PI-3K activity was decreased by pretreatment of cells with PTX. Finally, we have shown that the co-stimulation of cells with platelet-derived growth factor (PDGF) and S1P (which failed to stimulate DNA synthesis) elicited a larger p42/p44 MAPK activation over a 30 min stimulation compared with each agonist alone. This was associated with a S1P-dependent increase in PDGF-stimulated DNA synthesis. These results demonstrate that S1P activates c-Src and Grb-2-PI-3K (intermediates in the p42/p44 MAPK cascade) via a PTX-sensitive mechanism. This action of S1P is consistent with the stimulation of EDG-1 receptors. S1P might also function as a co-mitogen with PDGF, producing a more robust activation of a common permissive signal transduction pathway linked to DNA synthesis.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-7499260,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-7651538,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-7744787,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-7759503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-7781920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8442759,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8471632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8567663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8596637,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8645177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8665846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8849729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8896446,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8897440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-8994038,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9070858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9191154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9202044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9214627,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9384582,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9409733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9480864,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9488656,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9765227,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10051434-9882612
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-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, Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lysophospholipid,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine,
http://linkedlifedata.com/resource/pubmed/chemical/sphingosine 1-phosphate,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
338 ( Pt 3)
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
643-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10051434-Animals,
pubmed-meshheading:10051434-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:10051434-Cell Line,
pubmed-meshheading:10051434-Enzyme Activation,
pubmed-meshheading:10051434-Guinea Pigs,
pubmed-meshheading:10051434-Immediate-Early Proteins,
pubmed-meshheading:10051434-Lysophospholipids,
pubmed-meshheading:10051434-Muscle, Smooth,
pubmed-meshheading:10051434-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:10051434-Receptors, Cell Surface,
pubmed-meshheading:10051434-Receptors, G-Protein-Coupled,
pubmed-meshheading:10051434-Receptors, Growth Factor,
pubmed-meshheading:10051434-Receptors, Lysophospholipid,
pubmed-meshheading:10051434-Signal Transduction,
pubmed-meshheading:10051434-Sphingosine,
pubmed-meshheading:10051434-Trachea,
pubmed-meshheading:10051434-Transcriptional Activation,
pubmed-meshheading:10051434-src-Family Kinases
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pubmed:year |
1999
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pubmed:articleTitle |
Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle. Role of endothelial differentiation gene 1, c-Src tyrosine kinase and phosphoinositide 3-kinase.
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pubmed:affiliation |
Department of Physiology and Pharmacology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 ONR, Scotland, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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