Source:http://linkedlifedata.com/resource/pubmed/id/18721797
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2008-9-11
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphothreonine,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1090-2104
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
375
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
399-404
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18721797-Animals,
pubmed-meshheading:18721797-Cell Line,
pubmed-meshheading:18721797-Down-Regulation,
pubmed-meshheading:18721797-Hot Temperature,
pubmed-meshheading:18721797-Humans,
pubmed-meshheading:18721797-Mice,
pubmed-meshheading:18721797-PTEN Phosphohydrolase,
pubmed-meshheading:18721797-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18721797-Phosphoserine,
pubmed-meshheading:18721797-Phosphothreonine,
pubmed-meshheading:18721797-Proto-Oncogene Proteins c-akt
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pubmed:year |
2008
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pubmed:articleTitle |
Temperature sensitivity of phospho-Ser(473)-PKB/AKT.
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pubmed:affiliation |
Department of Radiation Oncology, University Hospital Zurich, CH-8091 Zurich, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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