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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
38
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pubmed:dateCreated |
2002-9-16
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pubmed:abstractText |
Normal cellular functions of hamartin and tuberin, encoded by the TSC1 and TSC2 tumor suppressor genes, are closely related to their direct interactions. However, the regulation of the hamartin-tuberin complex in the context of the physiologic role as tumor suppressor genes has not been documented. Here we show that insulin or insulin growth factor (IGF) 1 stimulates phosphorylation of tuberin, which is inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 but not by the mitogen-activated protein kinase inhibitor PD98059. Expression of constitutively active PI3K or active Akt, including Akt1 and Akt2, induces tuberin phosphorylation. We further demonstrate that Akt/PKB associates with hamartin-tuberin complexes, promoting phosphorylation of tuberin and increased degradation of hamartin-tuberin complexes. The ability to form complexes, however, is not blocked. Akt also inhibits tuberin-mediated degradation of p27(kip1), thereby promoting CDK2 activity and cellular proliferation. Our results indicate that tuberin is a direct physiological substrate of Akt and that phosphorylation of tuberin by PI3K/Akt is a major mechanism controlling hamartin-tuberin function.
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pubmed:grant |
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/AKT2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Akt2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/tuberous sclerosis complex 1 protein,
http://linkedlifedata.com/resource/pubmed/chemical/tuberous sclerosis complex 2 protein
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:ChengJin QJQ,
pubmed-author:FeldmanRichard IRI,
pubmed-author:HagenK SKS,
pubmed-author:HalleyDicky J JDJ,
pubmed-author:NellistMarkM,
pubmed-author:NicosiaSanto VSV,
pubmed-author:OuChien ChenCC,
pubmed-author:PledgerWarren JWJ,
pubmed-author:SuiXue-MeiXM,
pubmed-author:SunMeiM,
pubmed-author:YangLinL,
pubmed-author:YeungRaymond SRS
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35364-70
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12167664-Amino Acid Sequence,
pubmed-meshheading:12167664-Animals,
pubmed-meshheading:12167664-Blood,
pubmed-meshheading:12167664-Cell Line,
pubmed-meshheading:12167664-Genes, Tumor Suppressor,
pubmed-meshheading:12167664-Humans,
pubmed-meshheading:12167664-Hydrolysis,
pubmed-meshheading:12167664-Insulin,
pubmed-meshheading:12167664-Insulin-Like Growth Factor I,
pubmed-meshheading:12167664-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12167664-Phosphorylation,
pubmed-meshheading:12167664-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12167664-Proteins,
pubmed-meshheading:12167664-Proto-Oncogene Proteins,
pubmed-meshheading:12167664-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12167664-Rats,
pubmed-meshheading:12167664-Repressor Proteins,
pubmed-meshheading:12167664-Substrate Specificity,
pubmed-meshheading:12167664-Tumor Suppressor Proteins
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pubmed:year |
2002
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pubmed:articleTitle |
Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin.
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pubmed:affiliation |
Department of Pathology, Molecular Oncology, and Drug Discovery Programs, University of South Florida College of Medicine, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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