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rdf:type |
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lifeskim:mentions |
umls-concept:C0031715,
umls-concept:C0598086,
umls-concept:C0598388,
umls-concept:C0851285,
umls-concept:C1145667,
umls-concept:C1415887,
umls-concept:C1419040,
umls-concept:C1420010,
umls-concept:C1420433,
umls-concept:C1424666,
umls-concept:C1515877,
umls-concept:C1879547
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pubmed:issue |
6
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pubmed:dateCreated |
2008-6-23
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pubmed:abstractText |
The cell-cycle effects of mTORC1 are not fully understood. We provide evidence that mTOR-raptor phosphorylates SGK1 to modulate p27 function. Cellular mTOR activation, by refeeding of amino acid-deprived cells or by TSC2 shRNA, activated SGK1 and p27 phosphorylation at T157, and both were inhibited by short-term rapamycin treatment and by SGK1 shRNA. mTOR overexpression activated both Akt and SGK1, causing TGF-beta resistance through impaired nuclear import and cytoplasmic accumulation of p27. Rapamycin or raptor shRNA impaired mTOR-driven p70 and SGK1 activation, but not that of Akt, and decreased cytoplasmic p27. mTOR/raptor/SGK1 complexes were detected in cells. mTOR phosphorylated SGK1, but not SGK1-S422A, in vitro. SGK1 phosphorylated p27 in vitro. These data implicate SGK1 as an mTORC1 (mTOR-raptor) substrate. mTOR may promote G1 progression in part through SGK1 activation and deregulate the cell cycle in cancers through both Akt- and SGK-mediated p27 T157 phosphorylation and cytoplasmic p27 mislocalization.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proliferating Cell Nuclear Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/p27 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/serum-glucocorticoid regulated...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1097-4164
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
20
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
701-11
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:18570873-Cell Cycle,
pubmed-meshheading:18570873-Cell Line, Tumor,
pubmed-meshheading:18570873-Cell Nucleus,
pubmed-meshheading:18570873-Cytoplasm,
pubmed-meshheading:18570873-Enzyme Activation,
pubmed-meshheading:18570873-Homeostasis,
pubmed-meshheading:18570873-Humans,
pubmed-meshheading:18570873-Immediate-Early Proteins,
pubmed-meshheading:18570873-Kinetics,
pubmed-meshheading:18570873-Melanoma,
pubmed-meshheading:18570873-Phosphorylation,
pubmed-meshheading:18570873-Proliferating Cell Nuclear Antigen,
pubmed-meshheading:18570873-Protein Binding,
pubmed-meshheading:18570873-Protein Kinases,
pubmed-meshheading:18570873-Protein-Serine-Threonine Kinases,
pubmed-meshheading:18570873-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18570873-Recombinant Proteins,
pubmed-meshheading:18570873-TOR Serine-Threonine Kinases,
pubmed-meshheading:18570873-Transfection
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pubmed:year |
2008
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pubmed:articleTitle |
mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation.
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pubmed:affiliation |
Braman Family Breast Cancer Institute, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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