title: Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors.
abstract: The rate and extent of the agonist-dependent phosphorylation of beta 2-adrenergic receptors and rhodopsin by beta-adrenergic receptor kinase (beta ARK) are markedly enhanced on addition of G protein beta gamma subunits. With a model peptide substrate it was demonstrated that direct activation of the kinase could not account for this effect. G protein beta gamma subunits were shown to interact directly with the COOH-terminal region of beta ARK, and formation of this beta ARK-beta gamma complex resulted in receptor-facilitated membrane localization of the enzyme. The beta gamma subunits of transducin were less effective at both enhancing the rate of receptor phosphorylation and binding to the COOH-terminus of beta ARK, suggesting that the enzyme preferentially binds specific beta gamma complexes. The beta gamma-mediated membrane localization of beta ARK serves to intimately link receptor activation to beta ARK-mediated desensitization.
authors.affiliation: Howard Hughes Medical Research Institute, Department of Medicine, Duke University Medical Center, Durham, NC 27710.
authors.forename: J A
authors.initials: JA
authors.lastname: Pitcher
authors.forename: J
authors.initials: J
authors.lastname: Inglese
authors.forename: J B
authors.initials: JB
authors.lastname: Higgins
authors.forename: J L
authors.initials: JL
authors.lastname: Arriza
authors.forename: P J
authors.initials: PJ
authors.lastname: Casey
authors.forename: C
authors.initials: C
authors.lastname: Kim
authors.forename: J L
authors.initials: JL
authors.lastname: Benovic
authors.forename: M M
authors.initials: MM
authors.lastname: Kwatra
authors.forename: M G
authors.initials: MG
authors.lastname: Caron
authors.forename: R J
authors.initials: RJ
authors.lastname: Lefkowitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D017868:Cyclic AMP-Dependent Protein Kinases; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D019204:GTP-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012243:Rhodopsin / Q000378:metabolism; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D051552:beta-Adrenergic Receptor Kinases
chemical_list: D011943:Receptors, Adrenergic, beta; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; D012243:Rhodopsin; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D019204:GTP-Binding Proteins