Source:http://linkedlifedata.com/resource/pubmed/id/18006496
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2008-1-21
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| pubmed:abstractText |
Heptahelical G protein-coupled receptors employ several mechanisms to activate the ERK1/2 cascade and control gene transcription. Previous work with the angiotensin AT1a receptor has shown that G(q/11) activation leads to a rapid and transient rise in ERK1/2 activity, whereas beta-arrestin binding supports sustained ERK1/2 activation by scaffolding a Raf.MEK.ERK complex associated with the internalized receptor. In this study, we compared the role of the two beta-arrestin isoforms in AT1a receptor desensitization, ERK1/2 activation and transcription using selective RNA interference. In HEK293 cells, both the native AT1a receptor and a G protein-coupling deficient DRY/AAY mutant recruited beta-arrestin1 and beta-arrestin2 upon angiotensin binding and internalized with the receptor. In contrast, only beta-arrestin2 supported protein kinase C-independent ERK1/2 activation by both the AT1a and DRY/AAY receptors. Using focused gene expression filter arrays to screen for endogenous transcriptional responses, we found that silencing beta-arrestin1 or beta-arrestin2 individually did not alter the response pattern but that silencing both caused a marked increase in the number of transcripts that were significantly up-regulated in response to AT1a receptor activation. The DRY/AAY receptor failed to elicit any detectable transcriptional response despite its ability to stimulate beta-arrestin2-dependent ERK1/2 activation. These results indicate that the transcriptional response to AT1a receptor activation primarily reflects heterotrimeric G protein activation. Although beta-arrestin1 and beta-arrestin2 are functionally specialized with respect to supporting G protein-independent ERK1/2 activation, their common effect is to dampen the transcriptional response by promoting receptor desensitization.
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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/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Arrestins,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Angiotensin, Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents,
http://linkedlifedata.com/resource/pubmed/chemical/beta-arrestin,
http://linkedlifedata.com/resource/pubmed/chemical/raf Kinases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
25
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| pubmed:volume |
283
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2088-97
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:18006496-Angiotensin II,
pubmed-meshheading:18006496-Animals,
pubmed-meshheading:18006496-Arrestins,
pubmed-meshheading:18006496-Cell Line,
pubmed-meshheading:18006496-Enzyme Activation,
pubmed-meshheading:18006496-GTP-Binding Protein alpha Subunits, Gq-G11,
pubmed-meshheading:18006496-Gene Expression Profiling,
pubmed-meshheading:18006496-Humans,
pubmed-meshheading:18006496-MAP Kinase Kinase Kinases,
pubmed-meshheading:18006496-MAP Kinase Signaling System,
pubmed-meshheading:18006496-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:18006496-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:18006496-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:18006496-Protein Isoforms,
pubmed-meshheading:18006496-Rats,
pubmed-meshheading:18006496-Receptor, Angiotensin, Type 1,
pubmed-meshheading:18006496-Transcription, Genetic,
pubmed-meshheading:18006496-Up-Regulation,
pubmed-meshheading:18006496-Vasoconstrictor Agents,
pubmed-meshheading:18006496-raf Kinases
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| pubmed:year |
2008
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| pubmed:articleTitle |
Role of beta-arrestin-mediated desensitization and signaling in the control of angiotensin AT1a receptor-stimulated transcription.
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| pubmed:affiliation |
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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