Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-8622
Oehler-Jänne, C; von Bueren, A O; Vuong, V; Hollenstein, A; Grotzer, M A; Pruschy, M (2008). Temperature sensitivity of phospho-Ser(473)-PKB/AKT. Biochemical and Biophysical Research Communications (BBRC), 375(3):399-404.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Radiation Oncology|
04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
|DDC:||610 Medicine & health|
|Deposited On:||18 Dec 2008 15:28|
|Last Modified:||28 Nov 2013 02:39|
|Citations:||Web of Science®. Times Cited: 13|
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