Source:http://linkedlifedata.com/resource/pubmed/id/10393547
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
27
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| pubmed:dateCreated |
1999-8-2
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| pubmed:abstractText |
Previous studies with overexpressing wild-type or dominant negative nonvisual arrestins have established a role for these proteins in beta2-adrenergic receptor (beta2AR) internalization, desensitization, and resensitization. To validate and extend such findings, we employed an antisense strategy to target the nonvisual arrestins, arrestin-2 and arrestin-3, and determined the associated effects on the regulation of G protein-coupled receptor (GPCR) signaling. HEK293 cells stably expressing antisense constructs targeting arrestin-2 exhibited a selective reduction (approximately 50%) in arrestin-2 levels, while arrestin-3 antisense constructs resulted in reductions (>/=50%) in both arrestin-2 and arrestin-3 levels. Initial analysis of these cells demonstrated that a reduced level of arrestin expression resulted in a significant decrease in the extent of agonist-induced internalization of exogenously expressed beta2ARs, but had no effect on internalization of either m2 or m3 muscarinic acetylcholine receptors. Additional characterization involved assessing the role of arrestins in the regulation of endogenous GPCRs in these cells. Reduced arrestin levels significantly decreased the rate of endogenous beta2AR internalization, desensitization, and resensitization. Further analysis demonstrated that the desensitization of endogenous A2b adenosine and prostaglandin E2-stimulated receptors was also attenuated in cells with reduced arrestin levels. The effects on the beta2-adrenergic, A2b adenosine, and PGE2-stimulated receptors were similar among cell lines that exhibited either a selective reduction in arrestin-2 levels or a reduction in both arrestin-2 and -3 levels. These findings establish the utility of antisense approaches in the examination of arrestin-mediated GPCR regulation.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Arrestins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Muscarinic M2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Muscarinic M3,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Muscarinic,
http://linkedlifedata.com/resource/pubmed/chemical/arrestin3
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
6
|
| pubmed:volume |
38
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
8723-32
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:10393547-Adenylate Cyclase,
pubmed-meshheading:10393547-Adrenergic beta-2 Receptor Agonists,
pubmed-meshheading:10393547-Animals,
pubmed-meshheading:10393547-Arrestins,
pubmed-meshheading:10393547-COS Cells,
pubmed-meshheading:10393547-Cell Line, Transformed,
pubmed-meshheading:10393547-Cyclic AMP,
pubmed-meshheading:10393547-GTP-Binding Proteins,
pubmed-meshheading:10393547-Humans,
pubmed-meshheading:10393547-Kidney,
pubmed-meshheading:10393547-Oligonucleotides, Antisense,
pubmed-meshheading:10393547-Phosphoproteins,
pubmed-meshheading:10393547-RNA, Messenger,
pubmed-meshheading:10393547-Receptor, Muscarinic M2,
pubmed-meshheading:10393547-Receptor, Muscarinic M3,
pubmed-meshheading:10393547-Receptors, Adrenergic, beta-2,
pubmed-meshheading:10393547-Receptors, Cell Surface,
pubmed-meshheading:10393547-Receptors, Muscarinic,
pubmed-meshheading:10393547-Transfection
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| pubmed:year |
1999
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| pubmed:articleTitle |
Characterization of G protein-coupled receptor regulation in antisense mRNA-expressing cells with reduced arrestin levels.
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| pubmed:affiliation |
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, 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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