title: The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain.
abstract: The beta-adrenergic receptor kinase (beta ARK) phosphorylates the agonist-occupied beta-adrenergic receptor to promote rapid receptor uncoupling from Gs, thereby attenuating adenylyl cyclase activity. Beta ARK-mediated receptor desensitization may reflect a general molecular mechanism operative on many G-protein-coupled receptor systems and, particularly, synaptic neurotransmitter receptors. Two distinct cDNAs encoding beta ARK isozymes were isolated from rat brain and sequenced. The regional and cellular distributions of these two gene products, termed beta ARK1 and beta ARK2, were determined in brain by in situ hybridization and by immunohistochemistry at the light and electron microscopic levels. The beta ARK isozymes were found to be expressed primarily in neurons distributed throughout the CNS. Ultrastructurally, beta ARK1 and beta ARK2 immunoreactivities were present both in association with postsynaptic densities and, presynaptically, with axon terminals. The beta ARK isozymes have a regional and subcellular distribution consistent with a general role in the desensitization of synaptic receptors.
authors.affiliation: Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: J L
authors.initials: JL
authors.lastname: Arriza
authors.forename: T M
authors.initials: TM
authors.lastname: Dawson
authors.forename: R B
authors.initials: RB
authors.lastname: Simerly
authors.forename: L J
authors.initials: LJ
authors.lastname: Martin
authors.forename: M G
authors.initials: MG
authors.lastname: Caron
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
authors.forename: R J
authors.initials: RJ
authors.lastname: Lefkowitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D001923:Brain Chemistry; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*; D051552:beta-Adrenergic Receptor Kinases
chemical_list: D011506:Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D019204:GTP-Binding Proteins