|
|
ReportsTargeting of Diacylglycerol Degradation to M1 Muscarinic Receptors by ß-Arrestins
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 ß-arrestins coordinate both processes for the Gq-coupled M1 muscarinic receptor. ß-Arrestins physically interact with diacylglycerol kinases (DGKs), enzymes that degrade DAG. Moreover, ß-arrestins are essential for conversion of DAG to phosphatidic acid after agonist stimulation, and this activity requires recruitment of the ß-arrestin–DGK complex to activated 7TMRs. The dual function of ß-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 ß2-adrenergic receptors. Thus, ß-arrestins can serve similar regulatory functions for disparate classes of 7TMRs through structurally dissimilar enzymes that degrade chemically distinct second messengers.
1 Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. * Present address: Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
The editors suggest the following Related Resources on Science sites:In Science Magazine
In Science Signaling
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
|
To whom correspondence should be addressed. E-mail: 
Science. ISSN 0036-8075 (print), 1095-9203 (online)
Magazine | News | Signaling | Careers | Multimedia | Collections | Help | Site Map | RSS
Subscribe | Feedback | Privacy / Legal | About Us | Advertise With Us | Contact Us
© 2007 American Association for the Advancement of Science. All Rights Reserved.
AAAS is a partner of HINARI, AGORA, PatientInform, CrossRef, and COUNTER.
You have reached the bottom of the page. Back to top