Temperature sensitivity of phospho-Ser473-PKB/AKT
| Autor: | Van Vuong, Andreas Hollenstein, Michael A. Grotzer, Christoph Oehler-Jänne, André O. von Bueren, Martin Pruschy |
|---|---|
| Přispěvatelé: | University of Zurich, Pruschy, M |
| Rok vydání: | 2008 |
| Předmět: |
Hot Temperature
1303 Biochemistry Phosphatase Biophysics Down-Regulation 610 Medicine & health Biochemistry Cell Line 1307 Cell Biology Dephosphorylation Mice Phosphatidylinositol 3-Kinases Phosphoserine 1312 Molecular Biology Animals Humans PTEN Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway biology PTEN Phosphohydrolase Cell Biology Protein phosphatase 2 10044 Clinic for Radiation Oncology Cell biology Phosphothreonine 10036 Medical Clinic cardiovascular system biology.protein Cancer research Phosphorylation Signal transduction Proto-Oncogene Proteins c-akt 1304 Biophysics |
| Zdroj: | Biochemical and Biophysical Research Communications. 375:399-404 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2008.08.035 |
| Popis: | The phospho-PKB/Akt status is often used as surrogate marker to measure activation of the PI3K/Akt/mTOR signal transduction pathway. Though, inconsistencies of the p-Ser(473)-PKB/Akt status have raised doubts in the validity of p-Ser(473)-PKB/Akt phosphorylation as endpoint. Here, we determined that p-Ser(473)-PKB/Akt but not p-Thr(308)-PKB/Akt phosphorylation is highly temperature sensitive. p-Ser(473)-PKB/Akt phosphorylation was rapidly reduced to levels below 50% on exposure to 20-25 degrees C in murine and human cell lines including cells expressing constitutively active PI3K or lacking PTEN. Down-regulation of p-Ser(473)-PKB/Akt was reversible and re-exposure to physiological temperature resulted in increased p-Ser(473)-PKB/Akt phosphorylation levels. Phosphatase activity at low temperature was sustained at 75% baseline level and phosphatase inhibition prevented p-Ser(473)-PKB/Akt dephosphorylation induced by the low temperature shift. Interestingly temperature-dependent deregulation of the p-Ser(473)-PKB/Akt status was also observed in response to irradiation. Thus our data demonstrate that minimal additional stress factors deregulate the PI3K/Akt-survival pathway and the p-Ser(473)-PKB/Akt status as experimental endpoint. |
| Databáze: | OpenAIRE |
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