Source:http://linkedlifedata.com/resource/pubmed/id/10810294
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2000-6-21
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| pubmed:abstractText |
The interaction of GH, interleukin (IL)-6 and glucocorticoids is likely to be important in regulating the GH-insulin-like growth factor (IGF)-I axis. The signalling cascades activated by GH and IL-6 appear to be very similar, as demonstrated by studies using overexpression of the receptor and other components of the Jak-Stat and mitogen-activated protein (MAP) kinase pathways. Here we show that the human embryonic kidney cell line 293 (HEK293) expresses GH and IL-6 receptors endogenously. To determine which specific pathways might be activated by the two cytokines, at physiological levels of all components, we studied GH and IL-6 mediated signal transduction both under basal conditions and in the presence of overexpressed receptors and Stat proteins. Our results suggest a receptor specificity of Jak2 for GH receptors, and Jak1 for IL-6 receptors. Stat activation in response to GH and IL-6 was determined by reporter gene induction. Both GH and IL-6 were able to induce the reporter gene containing the Stat5 responsive element (LHRE) but the IL-6 response appeared to be mediated mainly through Stat3 activation. In contrast, the reporter gene containing the Stat3 responsive element (SIE) was IL-6 specific. The levels of gene induction by GH and IL-6 were not altered by the co-stimulation with GH and IL-6, suggesting that there is little cross-talk at the Jak-Stat activation level between the two cytokines. Neither GH nor IL-6 activated the MAP-kinase responsive serum response element (SRE), unless GH receptors or gp130 were overexpressed. Transfection of Stat3 or Stat5 expression vectors enhanced the response to GH and IL-6. Stimulation with dexamethasone synergistically enhanced GH activation of the LHRE reporter gene but had no effect on the IL-6 activation of the same reporter or on the SIE reporter gene. Thus, our studies suggest that while each cytokine, GH and IL-6, may activate various members of the Jak-Stat pathway in overexpression studies, specific activation of Stat3 by IL-6 and of Jak2 and Stat5 by GH can be observed in HEK293 cells and that in this system the synergistic effect of dexamethasone appears specific for Stat5.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/JAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/JAK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Milk Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Somatotropin,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/STAT5 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0022-0795
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
165
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
301-11
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10810294-Cell Line,
pubmed-meshheading:10810294-DNA-Binding Proteins,
pubmed-meshheading:10810294-Dexamethasone,
pubmed-meshheading:10810294-Enzyme Activation,
pubmed-meshheading:10810294-Glucocorticoids,
pubmed-meshheading:10810294-Growth Hormone,
pubmed-meshheading:10810294-Humans,
pubmed-meshheading:10810294-Interleukin-6,
pubmed-meshheading:10810294-Janus Kinase 1,
pubmed-meshheading:10810294-Janus Kinase 2,
pubmed-meshheading:10810294-Milk Proteins,
pubmed-meshheading:10810294-Protein-Tyrosine Kinases,
pubmed-meshheading:10810294-Proto-Oncogene Proteins,
pubmed-meshheading:10810294-RNA, Messenger,
pubmed-meshheading:10810294-Receptors, Interleukin-6,
pubmed-meshheading:10810294-Receptors, Somatotropin,
pubmed-meshheading:10810294-STAT3 Transcription Factor,
pubmed-meshheading:10810294-STAT5 Transcription Factor,
pubmed-meshheading:10810294-Signal Transduction,
pubmed-meshheading:10810294-Stimulation, Chemical,
pubmed-meshheading:10810294-Trans-Activators
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| pubmed:year |
2000
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| pubmed:articleTitle |
Stimulation of endogenous GH and interleukin-6 receptors selectively activates different Jaks and Stats, with a Stat5 specific synergistic effect of dexamethasone.
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| pubmed:affiliation |
Division of Clinical Sciences, University of Sheffield, UK. von.laue@necker.fr
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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