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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2000-5-16
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pubmed:abstractText |
Phosphorylation of G-protein-coupled receptors by second-messenger-stimulated kinases is central to the process of receptor desensitization [1-3]. Phosphorylation of the beta(2)-adrenergic receptor (beta(2)-AR) by protein kinase A (PKA), in addition to uncoupling adenylate cyclase activation, is obligatory for receptor-mediated activation of mitogen-activated protein kinase (MAP kinase) cascades [4] [5]. Although mechanisms for linking G-protein-coupled receptor kinases to the activated receptor are well established, analogous mechanisms for targeting second messenger kinases to the beta(2)-AR at the plasma membrane have not been elucidated. Here we show that the A-kinase-anchoring protein, AKAP79/150, co-precipitates with the beta(2)-AR in cell and tissue extracts, nucleating a signaling complex that includes PKA, protein kinase C (PKC) and protein phosphatase PP2B. The anchoring protein directly and constitutively interacts with the beta(2)-AR and promotes receptor phosphorylation following agonist stimulation. Functional studies show that PKA anchoring is required to enhance beta(2)-AR phosphorylation and to facilitate downstream activation of the MAP kinase pathway. This defines a role for AKAP79/150 in the recruitment of second-messenger-regulated signaling enzymes to a G-protein-coupled receptor.
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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/A Kinase Anchor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Akap5 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Calcineurin,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-2
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0960-9822
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
409-12
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:10753752-A Kinase Anchor Proteins,
pubmed-meshheading:10753752-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10753752-Adrenergic beta-2 Receptor Agonists,
pubmed-meshheading:10753752-Animals,
pubmed-meshheading:10753752-Brain,
pubmed-meshheading:10753752-Calcineurin,
pubmed-meshheading:10753752-Carrier Proteins,
pubmed-meshheading:10753752-Cell Membrane,
pubmed-meshheading:10753752-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:10753752-GTP-Binding Proteins,
pubmed-meshheading:10753752-MAP Kinase Signaling System,
pubmed-meshheading:10753752-Phosphorylation,
pubmed-meshheading:10753752-Precipitin Tests,
pubmed-meshheading:10753752-Protein Binding,
pubmed-meshheading:10753752-Rats,
pubmed-meshheading:10753752-Receptors, Adrenergic, beta-2,
pubmed-meshheading:10753752-Signal Transduction
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pubmed:year |
2000
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pubmed:articleTitle |
Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and signaling.
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pubmed:affiliation |
Howard Hughes Medical Institute, Vollum Institute L-474, Oregon Health Sciences University, Portland, 97201, 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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