Activation of Protein Kinase B/Akt Is Sufficient to Repress the Glucocorticoid and cAMP Induction of Phosphoenolpyruvate Carboxykinase Gene
| Autor: | Jinfang Liao, Kaname Nakatani, Richard A. Roth, Andreas Barthel |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
medicine.medical_specialty
Transcription Genetic Morpholines medicine.medical_treatment Endogeny Protein Serine-Threonine Kinases Biology Biochemistry Dexamethasone Cell Line Transcription (biology) Proto-Oncogene Proteins Internal medicine Cyclic AMP medicine Animals Insulin Drug Interactions Kinase activity Glucocorticoids Molecular Biology Protein kinase B Phosphoinositide-3 Kinase Inhibitors Sirolimus Dose-Response Relationship Drug Ribosomal Protein S6 Kinases Gluconeogenesis Cell Biology Transfection Rats Enzyme Activation Tamoxifen Endocrinology Liver Chromones Enzyme Repression Phosphoenolpyruvate carboxykinase Proto-Oncogene Proteins c-akt Phosphoenolpyruvate Carboxykinase (ATP) hormones hormone substitutes and hormone antagonists Glucocorticoid medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 273:27320-27324 |
| ISSN: | 0021-9258 |
| Popis: | A rat hepatoma cell line, H4IIE, was stably transfected with a tamoxifen regulatable Akt-1 construct. Treatment of these cells with tamoxifen caused a rapid stimulation of Akt enzymatic activity that was comparable with the activity observed with the endogenous Akt after insulin stimulation. Prior studies have extensively documented that insulin can repress the glucocorticoid and cAMP-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) gene transcription. Activation of this regulatable Akt with tamoxifen was found to mimic the dominant inhibitory effect of insulin on PEPCK gene transcription. Dose response curves to insulin and tamoxifen demonstrated that this response was very sensitive to Akt activation although the maximal response observed with tamoxifen activation was slightly less than that observed with insulin, indicating that the response to insulin may also involve other signaling cascades. The regulation of PEPCK transcription via Akt was, like that previously described for insulin, not dependent upon 70 kDa S6 kinase activity in that it was not inhibited by rapamycin. Finally, the expression of a kinase dead Akt was able to partially inhibit the ability of insulin to stimulate this response. In summary, the present results indicate that activation of Akt alone is sufficient to repress the glucocorticoid and cAMP-stimulated increase in PEPCK gene transcription. |
| Databáze: | OpenAIRE |
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