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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5524
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pubmed:dateCreated |
2001-6-15
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pubmed:databankReference |
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pubmed:abstractText |
Dysfunction of the tubby protein results in maturity-onset obesity in mice. Tubby has been implicated as a transcription regulator, but details of the molecular mechanism underlying its function remain unclear. Here we show that tubby functions in signal transduction from heterotrimeric GTP-binding protein (G protein)-coupled receptors. Tubby localizes to the plasma membrane by binding phosphatidylinositol 4,5-bisphosphate through its carboxyl terminal "tubby domain." X-ray crystallography reveals the atomic-level basis of this interaction and implicates tubby domains as phosphorylated-phosphatidyl- inositol binding factors. Receptor-mediated activation of G protein alphaq (Galphaq) releases tubby from the plasma membrane through the action of phospholipase C-beta, triggering translocation of tubby to the cell nucleus. The localization of tubby-like protein 3 (TULP3) is similarly regulated. These data suggest that tubby proteins function as membrane-bound transcription regulators that translocate to the nucleus in response to phosphoinositide hydrolysis, providing a direct link between G-protein signaling and the regulation of gene expression.
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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/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Heterotrimeric GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Localization Signals,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 4,5-Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C beta,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT2C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TULP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tub protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tulp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
292
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2041-50
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11375483-Active Transport, Cell Nucleus,
pubmed-meshheading:11375483-Amino Acid Sequence,
pubmed-meshheading:11375483-Animals,
pubmed-meshheading:11375483-Cell Membrane,
pubmed-meshheading:11375483-Cell Nucleus,
pubmed-meshheading:11375483-Cells, Cultured,
pubmed-meshheading:11375483-Crystallography, X-Ray,
pubmed-meshheading:11375483-GTP-Binding Protein alpha Subunits, Gq-G11,
pubmed-meshheading:11375483-Gene Expression Regulation,
pubmed-meshheading:11375483-Heterotrimeric GTP-Binding Proteins,
pubmed-meshheading:11375483-Humans,
pubmed-meshheading:11375483-Isoenzymes,
pubmed-meshheading:11375483-Membrane Lipids,
pubmed-meshheading:11375483-Mice,
pubmed-meshheading:11375483-Models, Biological,
pubmed-meshheading:11375483-Molecular Sequence Data,
pubmed-meshheading:11375483-Nuclear Localization Signals,
pubmed-meshheading:11375483-Obesity,
pubmed-meshheading:11375483-Phosphatidylinositol 4,5-Diphosphate,
pubmed-meshheading:11375483-Phosphatidylinositol Phosphates,
pubmed-meshheading:11375483-Phospholipase C beta,
pubmed-meshheading:11375483-Phosphorylation,
pubmed-meshheading:11375483-Protein Structure, Tertiary,
pubmed-meshheading:11375483-Proteins,
pubmed-meshheading:11375483-Receptor, Serotonin, 5-HT2C,
pubmed-meshheading:11375483-Receptors, Muscarinic,
pubmed-meshheading:11375483-Receptors, Serotonin,
pubmed-meshheading:11375483-Recombinant Fusion Proteins,
pubmed-meshheading:11375483-Signal Transduction,
pubmed-meshheading:11375483-Transcription Factors,
pubmed-meshheading:11375483-Type C Phospholipases
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pubmed:year |
2001
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pubmed:articleTitle |
G-protein signaling through tubby proteins.
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pubmed:affiliation |
Ruttenberg Cancer Center, Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine of New York University, 1425 Madison Avenue New York, NY 10029, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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