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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
37
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pubmed:dateCreated |
1994-10-11
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pubmed:abstractText |
Activation of cAMP-dependent protein kinase (cAPK) or protein kinase C (PKC) causes a rapid desensitization of beta 2-adrenergic receptor (beta AR) stimulation of adenylylcyclase in L cells, which previous studies suggest involves the cAPK/PKC consensus phosphorylation site in the third intracellular loop of the beta AR, RRSSK263. To determine the role of the individual serines in the cAPK- and PKC-mediated desensitizations, wild type (WT) and mutant beta ARs containing the substitutions, Ser261-->Ala, Ser262-->Ala, Ser262-->Asp, and Ser261/262-->Ala, were constructed and stably transfected into L cells. Results showed that serine 262 was the primary site of the cAPK-induced desensitization, whereas either serine 261 or serine 262 was sufficient to confer the 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA)/PKC-mediated desensitization. Coincident stimulation of cAPK and PKC caused an additive desensitization (6-8-fold increase in the EC50) which was significantly reduced (80%) only by the double substitution mutation. Quantitative evaluation of the coupling efficiencies and the GTP-shift of the WT and mutant receptors demonstrated that only one of the mutants, Ser262-->Ala, was partially uncoupled. The Ser262-->Asp mutation did not significantly uncouple, demonstrating that introducing a negative charge did not appear to mimic the desensitized state of the receptor. The beta AR expression level played a critical role in determining the pattern of beta AR desensitization; i.e. while the overall desensitization was unaltered within a large range of beta AR expression level (10-300 fmol/mg), the increase in EC50 and decrease in Vmax were differentially affected by the change in the receptor level.
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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/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
269
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
23032-8
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8083204-Adenylate Cyclase,
pubmed-meshheading:8083204-Amino Acid Sequence,
pubmed-meshheading:8083204-Animals,
pubmed-meshheading:8083204-Cricetinae,
pubmed-meshheading:8083204-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:8083204-Enzyme Activation,
pubmed-meshheading:8083204-L Cells (Cell Line),
pubmed-meshheading:8083204-Ligands,
pubmed-meshheading:8083204-Mice,
pubmed-meshheading:8083204-Molecular Sequence Data,
pubmed-meshheading:8083204-Mutation,
pubmed-meshheading:8083204-Protein Kinase C,
pubmed-meshheading:8083204-Receptors, Adrenergic, beta,
pubmed-meshheading:8083204-Recombinant Proteins
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pubmed:year |
1994
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pubmed:articleTitle |
cAMP-dependent protein kinase and protein kinase C consensus site mutations of the beta-adrenergic receptor. Effect on desensitization and stimulation of adenylylcyclase.
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pubmed:affiliation |
Graduate School of Biomedical Sciences, Department of Pharmacology, University of Texas Health Science Center at Houston 77225-0334.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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