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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-1-7
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pubmed:abstractText |
We previously reported that the beta(1)-adrenergic receptor (beta(1)AR) associates with PSD-95 through a PDZ domain-mediated interaction, by which PSD-95 modulates beta(1)AR function and facilitates the physical association of beta(1)AR with other synaptic proteins such as N-methyl-d-aspartate receptors. Here we demonstrate that beta(1)AR association with PSD-95 is regulated by G protein-coupled receptor kinase 5 (GRK5). When beta(1)AR and PSD-95 were coexpressed with either GRK2 or GRK5 in COS-7 cells, GRK5 alone dramatically decreased the association of beta(1)AR with PSD-95, although GRK2 and GRK5 both could be co-immunoprecipitated with beta(1)AR and both could enhance receptor phosphorylation in vivo. Increasing expression of GRK5 in the cells led to further decreased beta(1)AR association with PSD-95. Stimulation with the beta(1)AR agonist isoproterenol further decreased PSD-95 binding to beta(1)AR. In addition, GRK5 protein kinase activity was required for this regulatory effect since a kinase-inactive GRK5 mutant had no effect on PSD-95 binding to beta(1)AR. Moreover, the regulatory effect of GRK5 on beta(1)AR association with PSD-95 was observed only when GRK5 was expressed together with the receptor, but not when GRK5 was coexpressed with PSD-95. Thus, we propose that GRK5 regulates beta(1)AR association with PSD-95 through phosphorylation of beta(1)AR. Regulation of protein association through receptor phosphorylation may be a general mechanism used by G protein-coupled receptors that associate via PDZ domain-mediated protein/protein interactions.
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pubmed:grant |
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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/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Arrestins,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinase 5,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-1,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Adrenergic Receptor Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/beta-arrestin,
http://linkedlifedata.com/resource/pubmed/chemical/postsynaptic density proteins
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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 |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1607-13
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11700307-Adrenergic beta-Agonists,
pubmed-meshheading:11700307-Animals,
pubmed-meshheading:11700307-Arrestins,
pubmed-meshheading:11700307-COS Cells,
pubmed-meshheading:11700307-Culture Media, Serum-Free,
pubmed-meshheading:11700307-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:11700307-G-Protein-Coupled Receptor Kinase 5,
pubmed-meshheading:11700307-GTP-Binding Proteins,
pubmed-meshheading:11700307-Isoproterenol,
pubmed-meshheading:11700307-Nerve Tissue Proteins,
pubmed-meshheading:11700307-Phosphorylation,
pubmed-meshheading:11700307-Protein Binding,
pubmed-meshheading:11700307-Protein Structure, Tertiary,
pubmed-meshheading:11700307-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11700307-Receptors, Adrenergic, beta-1,
pubmed-meshheading:11700307-Recombinant Fusion Proteins,
pubmed-meshheading:11700307-Transfection,
pubmed-meshheading:11700307-beta-Adrenergic Receptor Kinases
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pubmed:year |
2002
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pubmed:articleTitle |
G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95.
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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.
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