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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2002-9-2
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pubmed:abstractText |
The direct mechanism by which the serine/threonine kinase Akt (also known as protein kinase B (PKB)) regulates cell growth is unknown. Here, we report that Drosophila melanogaster Akt/PKB stimulates growth by phosphorylating the tuberous sclerosis complex 2 (Tsc2) tumour suppressor and inhibiting formation of a Tsc1-Tsc2 complex. We show that Akt/PKB directly phosphorylates Drosophila Tsc2 in vitro at the conserved residues, Ser 924 and Thr 1518. Mutation of these sites renders Tsc2 insensitive to Akt/PKB signalling, increasing the stability of the Tsc1-Tsc2 complex within the cell. Stimulating Akt/PKB signalling in vivo markedly increases cell growth/size, disrupts the Tsc1-Tsc2 complex and disturbs the distinct subcellular localization of Tsc1 and Tsc2. Furthermore, all Akt/PKB growth signals are blocked by expression of a Tsc2 mutant lacking Akt phosphorylation sites. Thus, Tsc2 seems to be the critical target of Akt in mediating growth signals for the insulin signalling pathway.
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, Drosophila,
http://linkedlifedata.com/resource/pubmed/chemical/Drosophila Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
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 |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
658-65
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:12172554-Animals,
pubmed-meshheading:12172554-Binding Sites,
pubmed-meshheading:12172554-Cell Division,
pubmed-meshheading:12172554-Drosophila Proteins,
pubmed-meshheading:12172554-Drosophila melanogaster,
pubmed-meshheading:12172554-Eye,
pubmed-meshheading:12172554-Humans,
pubmed-meshheading:12172554-Insulin,
pubmed-meshheading:12172554-Models, Biological,
pubmed-meshheading:12172554-Mutagenesis, Site-Directed,
pubmed-meshheading:12172554-Phosphorylation,
pubmed-meshheading:12172554-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12172554-Proteins,
pubmed-meshheading:12172554-Proto-Oncogene Proteins,
pubmed-meshheading:12172554-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12172554-Repressor Proteins,
pubmed-meshheading:12172554-Signal Transduction,
pubmed-meshheading:12172554-Subcellular Fractions,
pubmed-meshheading:12172554-Tumor Suppressor Proteins
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pubmed:year |
2002
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pubmed:articleTitle |
Akt regulates growth by directly phosphorylating Tsc2.
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pubmed:affiliation |
Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536-0812, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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