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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2006-10-31
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pubmed:abstractText |
We identify a new mechanism for the beta(1)-adrenergic receptor (beta(1)AR)-mediated regulation of human ether-a-go-go-related gene (HERG) potassium channel (Kv11.1). We find that the previously reported modulatory interaction between Kv11.1 channels and 14-3-3epsilon proteins is competed by wild type beta(1)AR by means of a novel interaction between this receptor and 14-3-3epsilon. The association between beta(1)AR and 14-3-3epsilon is increased by agonist stimulation in both transfected cells and heart tissue and requires cAMP-dependent protein kinase (PKA) activity. The beta(1)AR/14-3-3epsilon association is direct, since it can be recapitulated using purified 14-3-3epsilon and beta(1)AR fusion proteins and is abolished in cells expressing beta(1)AR phosphorylation-deficient mutants. Biochemical and electrophysiological studies of the effects of isoproterenol on Kv11.1 currents recorded using the whole-cell patch clamp demonstrated that beta(1)AR phosphorylation-deficient mutants do not recruit 14-3-3epsilon away from Kv11.1 and display a markedly altered agonist-mediated modulation of Kv11.1 currents compared with wild-type beta(1)AR, increasing instead of inhibiting current amplitudes. Interestingly, such differential modulation is not observed in the presence of 14-3-3 inhibitors. Our results suggest that the dynamic association of 14-3-3 proteins to both beta(1)AR and Kv11.1 channels is involved in the adrenergic modulation of this critical regulator of cardiac repolarization and refractoriness.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-10224112,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-10493820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-10535961,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-10654934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-10715269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-10727525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-10836149,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-10837251,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-11178869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-11278781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-11562432,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-11799244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-11827686,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-11953308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-12196094,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-12591761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-12821660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-15023549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-15121159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-15122248,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-15221346,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-16336510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-7736582,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-7905023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-8601312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16914520-9428519
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/14-3-3 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/KCNV2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Voltage-Gated,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-1,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1059-1524
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4666-74
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16914520-14-3-3 Proteins,
pubmed-meshheading:16914520-Animals,
pubmed-meshheading:16914520-CHO Cells,
pubmed-meshheading:16914520-Cricetinae,
pubmed-meshheading:16914520-Cricetulus,
pubmed-meshheading:16914520-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:16914520-Guinea Pigs,
pubmed-meshheading:16914520-Heart,
pubmed-meshheading:16914520-Humans,
pubmed-meshheading:16914520-Ion Channel Gating,
pubmed-meshheading:16914520-Isoproterenol,
pubmed-meshheading:16914520-Mutant Proteins,
pubmed-meshheading:16914520-Mutation,
pubmed-meshheading:16914520-Phosphorylation,
pubmed-meshheading:16914520-Potassium Channels, Voltage-Gated,
pubmed-meshheading:16914520-Protein Binding,
pubmed-meshheading:16914520-Receptors, Adrenergic, beta-1,
pubmed-meshheading:16914520-Recombinant Proteins,
pubmed-meshheading:16914520-Time Factors
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pubmed:year |
2006
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pubmed:articleTitle |
Association of 14-3-3 proteins to beta1-adrenergic receptors modulates Kv11.1 K+ channel activity in recombinant systems.
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pubmed:affiliation |
Departamento de Biología Molecular and Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, 28049 Madrid, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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