Source:http://linkedlifedata.com/resource/pubmed/id/16051698
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2005-10-20
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| pubmed:abstractText |
beta-Arrestin is an adaptor protein that has been shown to couple G protein-coupled receptors (GPCRs) to clathrin-coated pits and target them for subsequent internalization. More recently, beta-arrestin 2 has also been shown to be involved in the activation of mitogen-activated protein kinase cascades by G protein-coupled receptors independently of G protein activation. Direct interactions between proteins can be monitored using enzyme complementation between two inactive deletion mutants of beta-galactosidase (beta-gal; Deltaalpha and Deltaomega). In the present study, we have used fusion proteins of the human beta(2)-adrenoceptor (C-terminal beta-gal Deltaalpha) and beta-arrestin 2 (beta-gal Deltaomega) to study directly the pharmacology of this interaction in C2C12 cells expressing the beta(2)-adrenoceptor-beta-gal Deltaalpha fusion protein at low physiological levels (38.2 +/- 2.7 fmol . mg protein(-1)). Isoprenaline, noradrenaline, and adrenaline (-log EC(50) = 5.9, 5.5, and 5.7, respectively) stimulated an association between the beta(2)-adrenoceptor and beta-arrestin 2 at much higher concentrations than required for activation of cAMP accumulation (-log EC(50) = 7.6, 6.3, and 7.7, respectively). This was sensitive to inhibition by the beta(2)-adrenoceptor antagonists propranolol, timolol, and ICI 118551. Both salbutamol and terbutaline behaved as partial agonists of beta-gal complementation. Furthermore, the long-acting beta(2)-agonist salmeterol (-log K(D) for inhibition of [(3)H]CGP12177 binding = 8.7) behaved as an antagonist of isoprenaline-stimulated beta(2)-adrenoceptor-arrestin 2 interactions (-log K(D) = 8.0), whereas acting as a full agonist of cAMP accumulation in the same cells (-log EC(50) = 9.2). These data suggest that salmeterol can discriminate between receptor-G(S) protein and receptor-arrestin 2 complexes (in terms of efficacy and affinity) in a way that is favorable for its long duration of action.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Albuterol,
http://linkedlifedata.com/resource/pubmed/chemical/Arrestins,
http://linkedlifedata.com/resource/pubmed/chemical/CGP 12177,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/ICI 118551,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Propanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/Propranolol,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase,
http://linkedlifedata.com/resource/pubmed/chemical/beta-arrestin,
http://linkedlifedata.com/resource/pubmed/chemical/salmeterol
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0022-3565
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
315
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
839-48
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16051698-Adrenergic beta-Agonists,
pubmed-meshheading:16051698-Adrenergic beta-Antagonists,
pubmed-meshheading:16051698-Albuterol,
pubmed-meshheading:16051698-Animals,
pubmed-meshheading:16051698-Arrestins,
pubmed-meshheading:16051698-CHO Cells,
pubmed-meshheading:16051698-Cell Line,
pubmed-meshheading:16051698-Cricetinae,
pubmed-meshheading:16051698-Cyclic AMP,
pubmed-meshheading:16051698-Forskolin,
pubmed-meshheading:16051698-Genetic Complementation Test,
pubmed-meshheading:16051698-Humans,
pubmed-meshheading:16051698-Isoproterenol,
pubmed-meshheading:16051698-Mutation,
pubmed-meshheading:16051698-Propanolamines,
pubmed-meshheading:16051698-Propranolol,
pubmed-meshheading:16051698-Receptors, Adrenergic, beta-2,
pubmed-meshheading:16051698-Recombinant Fusion Proteins,
pubmed-meshheading:16051698-Transfection,
pubmed-meshheading:16051698-beta-Galactosidase
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| pubmed:year |
2005
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| pubmed:articleTitle |
Characterization of isoprenaline- and salmeterol-stimulated interactions between beta2-adrenoceptors and beta-arrestin 2 using beta-galactosidase complementation in C2C12 cells.
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| pubmed:affiliation |
Institute of Cell Signaling, Medical School, Queen's Medical Centre, Nottingham, UK.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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