Source:http://linkedlifedata.com/resource/pubmed/id/10514456
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
42
|
| pubmed:dateCreated |
1999-11-19
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| pubmed:abstractText |
Following activation by ligand, most G protein-coupled receptors undergo rapid phosphorylation. This is accompanied by a drastic decrease in the efficacy of continued or repeated stimulation, due to receptor uncoupling from G protein and receptor internalization. Such processing steps have been shown to be absolutely dependent on receptor phosphorylation in the case of the N-formyl peptide receptor (FPR). In this study, we report results that indicate that the mechanisms responsible for desensitization and internalization are distinct. Using site-directed mutagenesis of the serine and threonine residues of the FPR carboxyl terminus, we have characterized regions that differentially regulate these two processes. Whereas substitution of all 11 Ser/Thr residues in the carboxyl terminus prevents both desensitization and internalization, substitution of four Ser/Thr residues between 328-332 blocks desensitization but has no effect on internalization. Similarly, substitution of four Ser/Thr residues between positions 334 and 339 results in a deficit in desensitization but again no decrease in internalization, suggesting that phosphorylation at either site evokes receptor internalization, whereas maximal desensitization requires phosphorylation at both sites. These results also indicate that receptor internalization is not involved in the process of desensitization. Further analysis of the residues between 328-332 revealed that restoration either of Ser(328) and Thr(329) or of Thr(331) and Ser(332) was sufficient to restore desensitization, suggesting that phosphorylation within either of these two sites, in addition to sites between residues 334 and 339, is sufficient to produce desensitization. Taken together, these results indicate that the mechanisms involved in FPR processing (uncoupling from G proteins and internalization) are regulated differentially by phosphorylation at distinct sites within the carboxyl terminus of the FPR. The relevance of this paradigm to other G protein-coupled receptors is discussed.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
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| pubmed:volume |
274
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
29791-5
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:10514456-Amino Acid Sequence,
pubmed-meshheading:10514456-Endocytosis,
pubmed-meshheading:10514456-Molecular Sequence Data,
pubmed-meshheading:10514456-Mutagenesis, Site-Directed,
pubmed-meshheading:10514456-Phosphorylation,
pubmed-meshheading:10514456-Protein Processing, Post-Translational,
pubmed-meshheading:10514456-Receptors, Formyl Peptide,
pubmed-meshheading:10514456-Receptors, Immunologic,
pubmed-meshheading:10514456-Receptors, Peptide,
pubmed-meshheading:10514456-Sequence Homology, Amino Acid
|
| pubmed:year |
1999
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| pubmed:articleTitle |
Differential phosphorylation paradigms dictate desensitization and internalization of the N-formyl peptide receptor.
|
| pubmed:affiliation |
Department of Cell Biology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131, 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
|