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Science 25 October 2002:
Vol. 298. no. 5594, pp. 834 - 836
DOI: 10.1126/science.1074683
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Reports

Targeting of Cyclic AMP Degradation to beta 2-Adrenergic Receptors by beta -Arrestins

Stephen J. Perry,1* George S. Baillie,2* Trudy A. Kohout,1* Ian McPhee,2dagger Maria M. Magiera,2 Kok Long Ang,3 William E. Miller,1 Alison J. McLean,2 Marco Conti,3 Miles D. Houslay,2 Robert J. Lefkowitz1ddagger

Catecholamines signal through the beta 2-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 beta 2-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.

1 Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
2 Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, G12 8QQ, UK.
3 Division of Reproductive Biology, Department of Gynecology and Obstetrics, Stanford University, School of Medicine, Stanford, CA 94305, USA.
*   These authors contributed equally to this work.

dagger    Present address: Scottish Biomedical, Todd Campus West of Scotland Science Park, Glasgow, Scotland, UK.

ddagger    To whom correspondence should be addressed. E-mail: lefko001{at}receptor-biol.duke.edu.

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