Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins.
Catecholamines signal through the beta2-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 beta2-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.
Perry, SJ; Baillie, GS; Kohout, TA; McPhee, I; Magiera, MM; Ang, KL; Miller, WE; McLean, AJ; Conti, M; Houslay, MD; Lefkowitz, RJ
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