Source:http://linkedlifedata.com/resource/pubmed/id/12962510
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
36
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| pubmed:dateCreated |
2003-9-9
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| pubmed:abstractText |
5-HT(2A) serotonin receptors represent the principal molecular targets for LSD-like hallucinogens and atypical antipsychotic drugs. It has been proposed that a dysregulation of 5-HT(2A) receptor-mediated signaling may contribute to the pathogenesis of schizophrenia and related diseases. A major mechanism for the attenuation of GPCR signaling following agonist activation typically involves the phosphorylation of serine and/or threonine residues by various kinases. Ser/Thr phosphorylation leads to the binding of accessory proteins and the uncoupling of the G proteins, thereby preventing further signaling. The molecular mechanisms by which 5-HT(2A) receptors are desensitized are unknown, and to date, no residues essential for agonist-mediated desensitization have been identified. Thus, we mutated, individually or in groups, all of the 37 serines and threonines in the cytoplasmic domains of the 5-HT(2A) receptor and assessed the effects of these mutations on agonist-mediated desensitization. We discovered that mutation of two residues, S421 in the C-terminal tail and S188 in the second intracellular loop, to alanine resulted in a significant block of agonist-induced desensitization. Intriguingly, a single-nucleotide polymorphism, of unreported frequency, at the S421 locus has been reported (S421F); the S421F mutation, like the S421A mutation, significantly attenuated agonist-mediated desensitization. Taken together, these findings indicate that the process of agonist-mediated desensitization of 5-HT(2A) receptors requires the presence of two nonconserved serine residues located in distinct intracellular loops.
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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/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbol Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositols,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Quipazine,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT2A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
16
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| pubmed:volume |
42
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
10853-62
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:12962510-Amino Acid Sequence,
pubmed-meshheading:12962510-Amino Acid Substitution,
pubmed-meshheading:12962510-Animals,
pubmed-meshheading:12962510-Cells, Cultured,
pubmed-meshheading:12962510-Enzyme Inhibitors,
pubmed-meshheading:12962510-Humans,
pubmed-meshheading:12962510-Molecular Sequence Data,
pubmed-meshheading:12962510-Phorbol Esters,
pubmed-meshheading:12962510-Phosphatidylinositols,
pubmed-meshheading:12962510-Protein Kinase C,
pubmed-meshheading:12962510-Quipazine,
pubmed-meshheading:12962510-Rats,
pubmed-meshheading:12962510-Receptor, Serotonin, 5-HT2A,
pubmed-meshheading:12962510-Receptors, Serotonin,
pubmed-meshheading:12962510-Recombinant Proteins,
pubmed-meshheading:12962510-Serine,
pubmed-meshheading:12962510-Serotonin,
pubmed-meshheading:12962510-Serotonin Receptor Agonists,
pubmed-meshheading:12962510-Threonine,
pubmed-meshheading:12962510-Transfection
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| pubmed:year |
2003
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| pubmed:articleTitle |
Identification of two serine residues essential for agonist-induced 5-HT2A receptor desensitization.
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| pubmed:affiliation |
Department of Biochemistry, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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