doi: 10.1126/science.1074683.
Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins
Affiliations
- PMID: 12399592
- DOI: 10.1126/science.1074683
Item in Clipboard
Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins
Science.
.
Abstract
Catecholamines signal through the beta2-adrenergic receptor by promoting production of the second messenger adenosine 3',5'-monophosphate (cAMP). The magnitude of this signal is restricted by desensitization of the receptors through their binding to beta-arrestins and by cAMP degradation by phosphodiesterase (PDE) enzymes. We show that beta-arrestins coordinate both processes by recruiting PDEs to activated beta2-adrenergic receptors in the plasma membrane of mammalian cells. In doing so, the beta-arrestins limit activation of membrane-associated cAMP-activated protein kinase by simultaneously slowing the rate of cAMP production through receptor desensitization and increasing the rate of its degradation at the membrane.
Similar articles
-
Salmeterol Efficacy and Bias in the Activation and Kinase-Mediated Desensitization of β2-Adrenergic Receptors.Mol Pharmacol. 2015 Jun;87(6):954-64. doi: 10.1124/mol.114.096800. Epub 2015 Mar 17. Mol Pharmacol. 2015. PMID: 25784721 Free PMC article.
-
RNA silencing identifies PDE4D5 as the functionally relevant cAMP phosphodiesterase interacting with beta arrestin to control the protein kinase A/AKAP79-mediated switching of the beta2-adrenergic receptor to activation of ERK in HEK293B2 cells.J Biol Chem. 2005 Sep 30;280(39):33178-89. doi: 10.1074/jbc.M414316200. Epub 2005 Jul 19. J Biol Chem. 2005. PMID: 16030021
-
Dynamic regulation, desensitization, and cross-talk in discrete subcellular microdomains during beta2-adrenoceptor and prostanoid receptor cAMP signaling.J Biol Chem. 2007 Nov 23;282(47):34235-49. doi: 10.1074/jbc.M706765200. Epub 2007 Sep 13. J Biol Chem. 2007. PMID: 17855344
-
The role of ERK2 docking and phosphorylation of PDE4 cAMP phosphodiesterase isoforms in mediating cross-talk between the cAMP and ERK signalling pathways.Biochem Soc Trans. 2003 Dec;31(Pt 6):1186-90. doi: 10.1042/bst0311186. Biochem Soc Trans. 2003. PMID: 14641023 Review.
-
cAMP-Specific phosphodiesterase-4 enzymes in the cardiovascular system: a molecular toolbox for generating compartmentalized cAMP signaling.Circ Res. 2007 Apr 13;100(7):950-66. doi: 10.1161/01.RES.0000261934.56938.38. Circ Res. 2007. PMID: 17431197 Review.
Cited by
-
The ins and outs of adrenergic signaling.J Mol Med (Berl). 2015 Sep;93(9):955-62. doi: 10.1007/s00109-015-1323-x. Epub 2015 Jul 23. J Mol Med (Berl). 2015. PMID: 26199112 Review.
-
Dimerization of cAMP phosphodiesterase-4 (PDE4) in living cells requires interfaces located in both the UCR1 and catalytic unit domains.Cell Signal. 2015 Apr;27(4):756-69. doi: 10.1016/j.cellsig.2014.12.009. Epub 2014 Dec 27. Cell Signal. 2015. PMID: 25546709 Free PMC article.
-
Special Issue on "New Advances in Cyclic AMP Signalling"-An Editorial Overview.Cells. 2020 Oct 12;9(10):2274. doi: 10.3390/cells9102274. Cells. 2020. PMID: 33053803 Free PMC article.
-
RACK1 and β-arrestin2 attenuate dimerization of PDE4 cAMP phosphodiesterase PDE4D5.Cell Signal. 2016 Jul;28(7):706-12. doi: 10.1016/j.cellsig.2015.08.003. Epub 2015 Aug 6. Cell Signal. 2016. PMID: 26257302 Free PMC article.
-
Multiple signalling pathways involved in beta2-adrenoceptor-mediated glucose uptake in rat skeletal muscle cells.Br J Pharmacol. 2006 Feb;147(4):446-54. doi: 10.1038/sj.bjp.0706626. Br J Pharmacol. 2006. PMID: 16415914 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
