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Targeting of Cyclic AMP Degradation to 2-Adrenergic Receptors by -Arrestins
Stephen J. Perry,1*George S. Baillie,2*Trudy A. Kohout,1*Ian McPhee,2Maria M. Magiera,2Kok Long Ang,3William E. Miller,1Alison J. McLean,2Marco Conti,3Miles D. Houslay,2Robert J. Lefkowitz1
Catecholamines signal through the
2-adrenergic receptor by promoting production of the
second messenger adenosine 3',5'-monophosphate(cAMP). The magnitude of
this signal is restricted by desensitizationof the receptors through
their binding to -arrestins and by cAMPdegradation by
phosphodiesterase (PDE) enzymes. We show that -arrestinscoordinate
both processes by recruiting PDEs to activated
2-adrenergicreceptors in the plasma membrane of
mammalian cells. In doingso, the -arrestins limit activation of
membrane-associated cAMP-activatedprotein kinase by simultaneously
slowing the rate of cAMP productionthrough receptor desensitization
and increasing the rate of itsdegradation 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.
Present address: Scottish Biomedical, Todd Campus West
of Scotland Science Park, Glasgow, Scotland, UK.
To whom correspondence should be addressed. E-mail:
lefko001{at}receptor-biol.duke.edu.
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2-Adrenergic Receptors by 
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 
