Source:http://linkedlifedata.com/resource/pubmed/id/17114809
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2007-1-8
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| pubmed:abstractText |
Tumor necrosis factor-alpha (TNF-alpha) has been shown to activate sphingosine kinase (SphK) in a variety of cell types. The extent to which SphK signaling mediates the pleiotropic effects of TNF-alpha is not entirely clear. The current study examined the role of SphK activity in TNF-alpha-stimulated cell proliferation in 1321N1 glioblastoma cells. We first demonstrated that pharmacological inhibitors of SphK markedly decrease TNF-alpha-stimulated DNA synthesis. Signaling mechanisms through which SphK mediated the effect of TNF-alpha on DNA synthesis were then examined. Inhibition of Rho proteins with C3 exoenzyme or of Rho kinase with Y27632 attenuated TNF-alpha-stimulated DNA synthesis. However, RhoA activation by TNF-alpha was not blocked by SphK inhibition. ERK activation was also required for TNF-alpha-stimulated DNA synthesis but likewise TNF-alpha-induced ERK activation was not blocked by inhibition of SphK. Thus, neither RhoA nor ERK activation are the SphK-dependent transducers of TNF-alpha-induced proliferation. In contrast, TNF-alpha-stimulated Akt phosphorylation, which was also required for DNA synthesis, was attenuated by SphK inhibition or SphK1 knockdown by small interfering RNA. Furthermore, cyclin D expression was increased by TNF-alpha in a SphK- and Akt-dependent manner. Additional studies demonstrated that TNF-alpha effects on DNA synthesis, ERK, and Akt phosphorylation are not mediated through cell surface Gi -coupled S1P receptors, because none of these responses were inhibited by pertussis toxin. We conclude that SphK-dependent Akt activation plays a significant role in TNF-alpha-induced cyclin D expression and cell proliferation.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lysosphingolipid,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/rho GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/sphingosine kinase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
12
|
| pubmed:volume |
282
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
863-70
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17114809-Brain Neoplasms,
pubmed-meshheading:17114809-Cell Division,
pubmed-meshheading:17114809-Cell Line, Tumor,
pubmed-meshheading:17114809-Cyclin D,
pubmed-meshheading:17114809-Cyclins,
pubmed-meshheading:17114809-DNA,
pubmed-meshheading:17114809-Enzyme Activation,
pubmed-meshheading:17114809-Glioblastoma,
pubmed-meshheading:17114809-Humans,
pubmed-meshheading:17114809-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:17114809-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17114809-RNA, Small Interfering,
pubmed-meshheading:17114809-Receptors, Cell Surface,
pubmed-meshheading:17114809-Receptors, Lysosphingolipid,
pubmed-meshheading:17114809-Signal Transduction,
pubmed-meshheading:17114809-Tumor Necrosis Factor-alpha,
pubmed-meshheading:17114809-rho GTP-Binding Proteins
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| pubmed:year |
2007
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| pubmed:articleTitle |
Tumor necrosis factor-alpha-stimulated cell proliferation is mediated through sphingosine kinase-dependent Akt activation and cyclin D expression.
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| pubmed:affiliation |
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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