Targeting of Cyclic AMP Degradation to$\beta_{2}-Adrenergic$Receptors by$\beta-Arrestins

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.