Publication Date:
2002-10-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Perry, Stephen J -- Baillie, George S -- Kohout, Trudy A -- McPhee, Ian -- Magiera, Maria M -- Ang, Kok Long -- Miller, William E -- McLean, Alison J -- Conti, Marco -- Houslay, Miles D -- Lefkowitz, Robert J -- HD20788/HD/NICHD NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2002 Oct 25;298(5594):834-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Medicine, 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/12399592" target="_blank"〉PubMed〈/a〉
Keywords:
3',5'-Cyclic-AMP Phosphodiesterases/genetics/metabolism
;
Adrenergic beta-Agonists/pharmacology
;
Animals
;
Arrestins/genetics/*metabolism
;
COS Cells
;
Cell Line
;
Cell Membrane/metabolism
;
Cyclic AMP/*metabolism
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Cyclic Nucleotide Phosphodiesterases, Type 4
;
Cytosol/metabolism
;
Humans
;
Isoenzymes/metabolism
;
Isoproterenol/pharmacology
;
Mice
;
Mutation
;
Precipitin Tests
;
Rats
;
Receptors, Adrenergic, beta-2/genetics/*metabolism
;
Recombinant Fusion Proteins/metabolism
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink