Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors

Science. 1992 Aug 28;257(5074):1264-7. doi: 10.1126/science.1325672.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cyclic AMP-Dependent Protein Kinases*
  • Dose-Response Relationship, Drug
  • Escherichia coli
  • GTP-Binding Proteins / physiology*
  • Gene Expression Regulation / drug effects
  • In Vitro Techniques
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Kinases / pharmacology*
  • Protein Processing, Post-Translational
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Adrenergic, beta / metabolism*
  • Recombinant Fusion Proteins
  • Rhodopsin / metabolism
  • Time Factors
  • Virulence Factors, Bordetella / pharmacology
  • beta-Adrenergic Receptor Kinases


  • Receptors, Adrenergic, beta
  • Recombinant Fusion Proteins
  • Virulence Factors, Bordetella
  • Rhodopsin
  • Protein Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • beta-Adrenergic Receptor Kinases
  • GTP-Binding Proteins