Temperature sensitivity of phospho-Ser(473)-PKB/AKT

Biochemical and Biophysical Research Communications
Christoph Oehler-JänneMartin Pruschy

Abstract

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.

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Citations

May 17, 2012·Cell Stress & Chaperones·Chad D TouchberryPhilip M Gallagher
Jan 12, 2011·The Journal of Physiological Sciences : JPS·Ryo KakigiShizuo Katamoto
Jul 10, 2013·The Journal of Physiological Sciences : JPS·Keiichi KoshinakaKentaro Kawanaka
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Mar 27, 2013·Analytical Chemistry·Alexandra J DickinsonNancy L Allbritton

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