title: Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Perry
authors.forename: George S
authors.initials: GS
authors.lastname: Baillie
authors.forename: Trudy A
authors.initials: TA
authors.lastname: Kohout
authors.forename: Ian
authors.initials: I
authors.lastname: McPhee
authors.forename: Maria M
authors.initials: MM
authors.lastname: Magiera
authors.forename: Kok Long
authors.initials: KL
authors.lastname: Ang
authors.forename: William E
authors.initials: WE
authors.lastname: Miller
authors.forename: Alison J
authors.initials: AJ
authors.lastname: McLean
authors.forename: Marco
authors.initials: M
authors.lastname: Conti
authors.forename: Miles D
authors.initials: MD
authors.lastname: Houslay
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lefkowitz
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D011233:Precipitin Tests; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D000071557:beta-Arrestins
chemical_list: D000318:Adrenergic beta-Agonists; D019390:Arrestins; D007527:Isoenzymes; D018343:Receptors, Adrenergic, beta-2; D011993:Recombinant Fusion Proteins; D000071557:beta-Arrestins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D007545:Isoproterenol