Stimulation of endogenous GH and interleukin-6 receptors selectively activates different Jaks and Stats, with a Stat5 specific synergistic effect of dexamethasone
| Autor: | Joëlle Finidori, Richard J. Ross, M. Maamra, S. Von Laue, Sue Justice, X. Y. Shen, P. R. M. Dobson |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_specialty Endocrinology Diabetes and Metabolism Dexamethasone Cell Line Endocrinology Proto-Oncogene Proteins Internal medicine STAT5 Transcription Factor medicine Humans RNA Messenger Receptor STAT3 Glucocorticoids STAT5 Reporter gene biology Janus kinase 1 Interleukin-6 Janus Kinase 1 Receptors Somatotropin Janus Kinase 2 Protein-Tyrosine Kinases Milk Proteins Glycoprotein 130 Receptors Interleukin-6 Stimulation Chemical DNA-Binding Proteins Enzyme Activation Growth Hormone Trans-Activators biology.protein STAT protein Signal transduction Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1479-6805 0022-0795 |
| DOI: | 10.1677/joe.0.1650301 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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