pubmed-article:11533056 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:11533056 | lifeskim:mentions | umls-concept:C0597357 | lld:lifeskim |
pubmed-article:11533056 | lifeskim:mentions | umls-concept:C0001492 | lld:lifeskim |
pubmed-article:11533056 | lifeskim:mentions | umls-concept:C0237753 | lld:lifeskim |
pubmed-article:11533056 | lifeskim:mentions | umls-concept:C0013682 | lld:lifeskim |
pubmed-article:11533056 | lifeskim:mentions | umls-concept:C0597359 | lld:lifeskim |
pubmed-article:11533056 | pubmed:issue | 45 | lld:pubmed |
pubmed-article:11533056 | pubmed:dateCreated | 2001-11-5 | lld:pubmed |
pubmed-article:11533056 | pubmed:abstractText | Recent evidence suggests that many signaling molecules localize in microdomains of the plasma membrane, particularly caveolae. In this study, overexpression of adenylyl cyclase was used as a functional probe of G protein-coupled receptor (GPCR) compartmentation. We found that three endogenous receptors in neonatal rat cardiomyocytes couple with different levels of efficiency to the activation of adenylyl cyclase type 6 (AC6), which localizes to caveolin-rich membrane fractions. Overexpression of AC6 enhanced the maximal cAMP response to beta(1)-adrenergic receptor (beta(1)AR)-selective activation 3.7-fold, to beta(2)AR-selective activation only 1.6-fold and to prostaglandin E(2) (PGE(2)) not at all. Therefore, the rank order of efficacy in coupling to AC6 is beta(1)AR > beta(2)AR > prostaglandin E(2) receptor (EP(2)R). beta(2)AR coupling efficiency was greater when we overexpressed the receptor or blocked its desensitization by expressing betaARKct, an inhibitor of G protein-coupled receptor kinase activation, but was not significantly greater when cells were treated with pertussis toxin. Assessment of receptor and AC expression indicated co-localization of AC5/6, beta(1)AR, and beta(2)AR, but not EP(2)R, in caveolin-rich membranes and caveolin-3 immunoprecipitates, likely explaining the observed activation of AC6 by betaAR subtypes but lack thereof by PGE(2). When cardiomyocytes were stimulated with a betaAR agonist, beta(2)AR were no longer found in caveolin-3 immunoprecipitates; an effect that was blocked by expression of betaARKct. Thus, agonist-induced translocation of beta(2)AR out of caveolae causes a sequestration of receptor from effector and likely contributes to the lower efficacy of beta(2)AR coupling to AC6 as compared with beta(1)AR, which do not similarly translocate. Therefore, spatial co-localization is a key determinant of efficiency of coupling by particular extracellular signals to activation of GPCR-linked effectors. | lld:pubmed |
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pubmed-article:11533056 | pubmed:language | eng | lld:pubmed |
pubmed-article:11533056 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:11533056 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:11533056 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:11533056 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:11533056 | pubmed:month | Nov | lld:pubmed |
pubmed-article:11533056 | pubmed:issn | 0021-9258 | lld:pubmed |
pubmed-article:11533056 | pubmed:author | pubmed-author:InselP APA | lld:pubmed |
pubmed-article:11533056 | pubmed:author | pubmed-author:ReganJ WJW | lld:pubmed |
pubmed-article:11533056 | pubmed:author | pubmed-author:XiangYY | lld:pubmed |
pubmed-article:11533056 | pubmed:author | pubmed-author:OstromR SRS | lld:pubmed |
pubmed-article:11533056 | pubmed:author | pubmed-author:GregorianCC | lld:pubmed |
pubmed-article:11533056 | pubmed:author | pubmed-author:DrenanR MRM | lld:pubmed |
pubmed-article:11533056 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:11533056 | pubmed:day | 9 | lld:pubmed |
pubmed-article:11533056 | pubmed:volume | 276 | lld:pubmed |
pubmed-article:11533056 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:11533056 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:11533056 | pubmed:pagination | 42063-9 | lld:pubmed |
pubmed-article:11533056 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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pubmed-article:11533056 | pubmed:year | 2001 | lld:pubmed |
pubmed-article:11533056 | pubmed:articleTitle | Receptor number and caveolar co-localization determine receptor coupling efficiency to adenylyl cyclase. | lld:pubmed |
pubmed-article:11533056 | pubmed:affiliation | Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA. | lld:pubmed |
pubmed-article:11533056 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:11533056 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
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