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rdf:type |
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lifeskim:mentions |
umls-concept:C0109317,
umls-concept:C0597357,
umls-concept:C0752312,
umls-concept:C0851285,
umls-concept:C1150579,
umls-concept:C1333340,
umls-concept:C1366882,
umls-concept:C1370600,
umls-concept:C1705767,
umls-concept:C1705791,
umls-concept:C1825351,
umls-concept:C1879547
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pubmed:issue |
28
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pubmed:dateCreated |
2003-7-4
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pubmed:abstractText |
Beta1-adrenergic receptors, expressed at high levels in the human heart, have a carboxyl-terminal ESKV motif that can directly interact with PDZ domain-containing proteins. Using the beta1-adrenergic receptor carboxyl terminus as bait, we identified the novel beta1-adrenergic receptor-binding partner GIPC in a yeast two-hybrid screen of a human heart cDNA library. Here we demonstrate that the PDZ domain-containing protein, GIPC, co-immunoprecipitates with the beta1-adrenergic receptor in COS-7 cells. Essential for this interaction is the Ser residue of the beta1-adrenergic receptor carboxyl-terminal ESKV motif. Our data also demonstrate that beta1-adrenergic receptor stimulation activates the mitogen-activated protein kinase, ERK1/2. beta1-adrenergic receptor-mediated ERK1/2 activation was inhibited by pertussis toxin, implicating Gi, and was substantially decreased by the expression of GIPC. Expression of GIPC had no observable effect on beta1-adrenergic receptor sequestration or receptor-mediated cAMP accumulation. This GIPC effect was specific for the beta1-adrenergic receptor and was dependent on an intact PDZ binding motif. These data suggest that GIPC can regulate beta1-adrenergic receptor-stimulated, Gi-mediated, ERK activation while having no effect on receptor internalization or Gs-mediated cAMP signaling.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/GIPC1 protein, human,
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/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-1,
http://linkedlifedata.com/resource/pubmed/chemical/Serine
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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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 |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26295-301
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12724327-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12724327-Amino Acid Motifs,
pubmed-meshheading:12724327-Animals,
pubmed-meshheading:12724327-COS Cells,
pubmed-meshheading:12724327-Carrier Proteins,
pubmed-meshheading:12724327-Cell Line,
pubmed-meshheading:12724327-Cyclic AMP,
pubmed-meshheading:12724327-DNA, Complementary,
pubmed-meshheading:12724327-Dose-Response Relationship, Drug,
pubmed-meshheading:12724327-Enzyme Activation,
pubmed-meshheading:12724327-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:12724327-Gene Library,
pubmed-meshheading:12724327-Humans,
pubmed-meshheading:12724327-Immunoblotting,
pubmed-meshheading:12724327-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12724327-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12724327-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12724327-Myocardium,
pubmed-meshheading:12724327-Neuropeptides,
pubmed-meshheading:12724327-Phosphorylation,
pubmed-meshheading:12724327-Plasmids,
pubmed-meshheading:12724327-Precipitin Tests,
pubmed-meshheading:12724327-Protein Binding,
pubmed-meshheading:12724327-Protein Structure, Tertiary,
pubmed-meshheading:12724327-Receptors, Adrenergic, beta-1,
pubmed-meshheading:12724327-Serine,
pubmed-meshheading:12724327-Signal Transduction,
pubmed-meshheading:12724327-Time Factors,
pubmed-meshheading:12724327-Transfection,
pubmed-meshheading:12724327-Two-Hybrid System Techniques
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pubmed:year |
2003
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pubmed:articleTitle |
GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation.
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pubmed:affiliation |
Howard Hughes Medical Institute, 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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