Targeting of cyclic AMP degradation to β2-adrenergic receptors by β-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 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.