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rdf:type |
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lifeskim:mentions |
umls-concept:C0000894,
umls-concept:C0022702,
umls-concept:C0037083,
umls-concept:C0086376,
umls-concept:C0182953,
umls-concept:C0205314,
umls-concept:C0243192,
umls-concept:C0376315,
umls-concept:C0439855,
umls-concept:C0597357,
umls-concept:C0679622,
umls-concept:C0681841,
umls-concept:C1710082,
umls-concept:C1879547
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pubmed:issue |
14
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pubmed:dateCreated |
2005-4-4
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pubmed:abstractText |
Regulators of G-protein signaling (RGS) proteins modulate signaling through heterotrimeric G-proteins. They act to enhance the intrinsic GTPase activity of the Galpha subunit but paradoxically have also been shown to enhance receptor-stimulated activation. To study this paradox, we used a G-protein gated K+ channel to report the dynamics of the G-protein cycle and fluorescence resonance energy transfer techniques with cyan and yellow fluorescent protein-tagged proteins to report physical interaction. Our data show that the acceleration of the activation kinetics is dissociated from deactivation kinetics and dependent on receptor and RGS type, G-protein isoform, and RGS expression levels. By using fluorescently tagged proteins, fluorescence resonance energy transfer microscopy showed a stable physical interaction between the G-protein alpha subunit and RGS (RGS8 and RGS7) that is independent of the functional state of the G-protein. RGS8 does not directly interact with G-protein-coupled receptors. Our data show participation of the RGS in the ternary complex between agonist-receptor and G-protein to form a "quaternary complex." Thus we propose a novel model for the action of RGS proteins in the G-protein cycle in which the RGS protein appears to enhance the "kinetic efficacy" of the ternary complex, by direct association with the G-protein alpha subunit.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13383-94
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15677457-Cell Line,
pubmed-meshheading:15677457-Fluorescence Resonance Energy Transfer,
pubmed-meshheading:15677457-G Protein-Coupled Inwardly-Rectifying Potassium Channels,
pubmed-meshheading:15677457-GTP-Binding Protein alpha Subunits,
pubmed-meshheading:15677457-GTP-Binding Proteins,
pubmed-meshheading:15677457-Humans,
pubmed-meshheading:15677457-Multiprotein Complexes,
pubmed-meshheading:15677457-Patch-Clamp Techniques,
pubmed-meshheading:15677457-Potassium Channels, Inwardly Rectifying,
pubmed-meshheading:15677457-Protein Isoforms,
pubmed-meshheading:15677457-Protein Structure, Quaternary,
pubmed-meshheading:15677457-RGS Proteins,
pubmed-meshheading:15677457-Recombinant Fusion Proteins,
pubmed-meshheading:15677457-Signal Transduction,
pubmed-meshheading:15677457-Subcellular Fractions
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pubmed:year |
2005
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pubmed:articleTitle |
Regulators of G-protein signaling form a quaternary complex with the agonist, receptor, and G-protein. A novel explanation for the acceleration of signaling activation kinetics.
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pubmed:affiliation |
BHF Laboratories and Department of Medicine, University College London, Room 420, 4th Floor, 5 University Street, London WC1E 6JJ, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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