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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2002-9-25
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pubmed:abstractText |
The PTEN/PI3K signaling pathway regulates a vast array of fundamental cellular responses. We show that cardiomyocyte-specific inactivation of tumor suppressor PTEN results in hypertrophy, and unexpectedly, a dramatic decrease in cardiac contractility. Analysis of double-mutant mice revealed that the cardiac hypertrophy and the contractility defects could be genetically uncoupled. PI3Kalpha mediates the alteration in cell size while PI3Kgamma acts as a negative regulator of cardiac contractility. Mechanistically, PI3Kgamma inhibits cAMP production and hypercontractility can be reverted by blocking cAMP function. These data show that PTEN has an important in vivo role in cardiomyocyte hypertrophy and GPCR signaling and identify a function for the PTEN-PI3Kgamma pathway in the modulation of heart muscle contractility.
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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/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoric Monoester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
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/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/zinterol
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0092-8674
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pubmed:author |
pubmed-author:BackxPeter HPH,
pubmed-author:BenovicJeffery LJL,
pubmed-author:ChengHai-Ying MHY,
pubmed-author:CrackowerMichael AMA,
pubmed-author:FrattaLuigiL,
pubmed-author:HirschEmilioE,
pubmed-author:Irie-SasakiJunkoJ,
pubmed-author:IzumoSeigoS,
pubmed-author:KahnC RonaldCR,
pubmed-author:KozieradzkiIvonaI,
pubmed-author:LemboGiuseppeG,
pubmed-author:Oliveira-dos-SantosAntonio JAJ,
pubmed-author:OuditGavin YGY,
pubmed-author:PenningerJosef MJM,
pubmed-author:RybinVitalyi OVO,
pubmed-author:SahRajanR,
pubmed-author:SaraoRenuR,
pubmed-author:SasakiTakehikoT,
pubmed-author:ShioiTetsuoT,
pubmed-author:SteinbergSusan FSF,
pubmed-author:SunHuiH,
pubmed-author:SuzukiAkiraA,
pubmed-author:WymannMatthias PMP
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
110
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
737-49
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12297047-Adrenergic beta-Agonists,
pubmed-meshheading:12297047-Animals,
pubmed-meshheading:12297047-Cardiomegaly,
pubmed-meshheading:12297047-Cell Size,
pubmed-meshheading:12297047-Cells, Cultured,
pubmed-meshheading:12297047-Cyclic AMP,
pubmed-meshheading:12297047-Dose-Response Relationship, Drug,
pubmed-meshheading:12297047-Ethanolamines,
pubmed-meshheading:12297047-GTP-Binding Proteins,
pubmed-meshheading:12297047-Gene Expression Regulation,
pubmed-meshheading:12297047-Genes, Tumor Suppressor,
pubmed-meshheading:12297047-Mice,
pubmed-meshheading:12297047-Mice, Mutant Strains,
pubmed-meshheading:12297047-Mice, Transgenic,
pubmed-meshheading:12297047-Myocardial Contraction,
pubmed-meshheading:12297047-Myocardium,
pubmed-meshheading:12297047-PTEN Phosphohydrolase,
pubmed-meshheading:12297047-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12297047-Phosphoric Monoester Hydrolases,
pubmed-meshheading:12297047-Phosphorylation,
pubmed-meshheading:12297047-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12297047-Proto-Oncogene Proteins,
pubmed-meshheading:12297047-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:12297047-Signal Transduction,
pubmed-meshheading:12297047-Tumor Suppressor Proteins
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pubmed:year |
2002
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pubmed:articleTitle |
Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways.
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pubmed:affiliation |
IMBA, Institute for Molecular Biotechnology of the Austrian Academy of Sciences, c/o Dr. Bohr Gasse 7, A-1030, Vienna, Austria.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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