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

Abstract

Catecholamines signal through the β₂-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 β-arrestins and by cAMP degradation by phosphodiesterase (PDE) enzymes. We show that β-arrestins coordinate both processes by recruiting PDEs to activated β₂-adrenergic receptors in the plasma membrane of mammalian cells. In doing so, the β-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.