Source:http://linkedlifedata.com/resource/pubmed/id/12473660
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0109317,
umls-concept:C0205245,
umls-concept:C0205360,
umls-concept:C0441712,
umls-concept:C0686907,
umls-concept:C0752312,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1704675,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1879547
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| pubmed:issue |
8
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| pubmed:dateCreated |
2003-2-17
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| pubmed:abstractText |
By binding to agonist-activated G protein-coupled receptors (GPCRs), beta-arrestins mediate homologous receptor desensitization and endocytosis via clathrin-coated pits. Recent data suggest that beta-arrestins also contribute to GPCR signaling by acting as scaffolds for components of the ERK mitogen-activated protein kinase cascade. Because of these dual functions, we hypothesized that the stability of the receptor-beta-arrestin interaction might affect the mechanism and functional consequences of GPCR-stimulated ERK activation. In transfected COS-7 cells, we found that angiotensin AT1a and vasopressin V2 receptors, which form stable receptor-beta-arrestin complexes, activated a beta-arrestin-bound pool of ERK2 more efficiently than alpha 1b and beta2 adrenergic receptors, which form transient receptor-beta-arrestin complexes. We next studied chimeric receptors in which the pattern of beta-arrestin binding was reversed by exchanging the C-terminal tails of the beta2 and V2 receptors. The ability of the V2 beta 2 and beta 2V2 chimeras to activate beta-arrestin-bound ERK2 corresponded to the pattern of beta-arrestin binding, suggesting that the stability of the receptor-beta-arrestin complex determined the mechanism of ERK2 activation. Analysis of covalently cross-linked detergent lysates and cellular fractionation revealed that wild type V2 receptors generated a larger pool of cytosolic phospho-ERK1/2 and less nuclear phospho-ERK1/2 than the chimeric V2 beta 2 receptor, consistent with the cytosolic retention of beta-arrestin-bound ERK. In stably transfected HEK-293 cells, the V2 beta 2 receptor increased ERK1/2-mediated, Elk-1-driven transcription of a luciferase reporter to a greater extent than the wild type V2 receptor. Furthermore, the V2 beta 2, but not the V2 receptor, was capable of eliciting a mitogenic response. These data suggest that the C-terminal tail of a GPCR, by determining the stability of the receptor-beta-arrestin complex, controls the extent of beta-arrestin-bound ERK activation, and influences both the subcellular localization of activated ERK and the physiologic consequences of ERK activation.
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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/Arrestins,
http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vasopressins,
http://linkedlifedata.com/resource/pubmed/chemical/beta-arrestin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
21
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| pubmed:volume |
278
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6258-67
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:12473660-Animals,
pubmed-meshheading:12473660-Arrestins,
pubmed-meshheading:12473660-COS Cells,
pubmed-meshheading:12473660-Cercopithecus aethiops,
pubmed-meshheading:12473660-Epidermal Growth Factor,
pubmed-meshheading:12473660-GTP-Binding Proteins,
pubmed-meshheading:12473660-Green Fluorescent Proteins,
pubmed-meshheading:12473660-Kinetics,
pubmed-meshheading:12473660-Luminescent Proteins,
pubmed-meshheading:12473660-MAP Kinase Signaling System,
pubmed-meshheading:12473660-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12473660-Models, Biological,
pubmed-meshheading:12473660-Phosphorylation,
pubmed-meshheading:12473660-Receptors, Cell Surface,
pubmed-meshheading:12473660-Recombinant Fusion Proteins,
pubmed-meshheading:12473660-Recombinant Proteins,
pubmed-meshheading:12473660-Signal Transduction,
pubmed-meshheading:12473660-Transfection,
pubmed-meshheading:12473660-Vasopressins
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| pubmed:year |
2003
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| pubmed:articleTitle |
The stability of the G protein-coupled receptor-beta-arrestin interaction determines the mechanism and functional consequence of ERK activation.
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| pubmed:affiliation |
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, 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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