Publication Date:
2007-02-03
Description:
Seven-transmembrane receptor (7TMR) signaling is transduced by second messengers such as diacylglycerol (DAG) generated in response to the heterotrimeric guanine nucleotide-binding protein Gq and is terminated by receptor desensitization and degradation of the second messengers. We show that beta-arrestins coordinate both processes for the Gq-coupled M1 muscarinic receptor. beta-Arrestins physically interact with diacylglycerol kinases (DGKs), enzymes that degrade DAG. Moreover, beta-arrestins are essential for conversion of DAG to phosphatidic acid after agonist stimulation, and this activity requires recruitment of the beta-arrestin-DGK complex to activated 7TMRs. The dual function of beta-arrestins, limiting production of diacylglycerol (by receptor desensitization) while enhancing its rate of degradation, is analogous to their ability to recruit adenosine 3',5'-monophosphate phosphodiesterases to Gs-coupled beta2-adrenergic receptors. Thus, beta-arrestins can serve similar regulatory functions for disparate classes of 7TMRs through structurally dissimilar enzymes that degrade chemically distinct second messengers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nelson, Christopher D -- Perry, Stephen J -- Regier, Debra S -- Prescott, Stephen M -- Topham, Matthew K -- Lefkowitz, Robert J -- CA95463/CA/NCI NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- HL70631/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):663-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272726" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Arrestins/*metabolism
;
COS Cells
;
Carbachol/pharmacology
;
Cell Line
;
Cercopithecus aethiops
;
Diacylglycerol Kinase/genetics/*metabolism
;
Diglycerides/*metabolism
;
Humans
;
Mutation
;
Phosphatidic Acids/metabolism
;
Protein Binding
;
RNA, Small Interfering
;
Receptor, Muscarinic M1/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Second Messenger Systems
;
*Signal Transduction
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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