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

Publication ,  Journal Article
Pitcher, JA; Inglese, J; Higgins, JB; Arriza, JL; Casey, PJ; Kim, C; Benovic, JL; Kwatra, MM; Caron, MG; Lefkowitz, RJ
Published in: Science
August 28, 1992

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.

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Published In

Science

DOI

ISSN

0036-8075

Publication Date

August 28, 1992

Volume

257

Issue

5074

Start / End Page

1264 / 1267

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Virulence Factors, Bordetella
  • Time Factors
  • Rhodopsin
  • Recombinant Fusion Proteins
  • Receptors, Adrenergic, beta
  • Protein Processing, Post-Translational
  • Protein Kinases
  • Phosphorylation
  • Molecular Sequence Data
 

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Pitcher, J. A., Inglese, J., Higgins, J. B., Arriza, J. L., Casey, P. J., Kim, C., … Lefkowitz, R. J. (1992). Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors. Science, 257(5074), 1264–1267. https://doi.org/10.1126/science.1325672
Pitcher, J. A., J. Inglese, J. B. Higgins, J. L. Arriza, P. J. Casey, C. Kim, J. L. Benovic, M. M. Kwatra, M. G. Caron, and R. J. Lefkowitz. “Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors.Science 257, no. 5074 (August 28, 1992): 1264–67. https://doi.org/10.1126/science.1325672.
Pitcher JA, Inglese J, Higgins JB, Arriza JL, Casey PJ, Kim C, et al. 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.
Pitcher, J. A., et al. “Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors.Science, vol. 257, no. 5074, Aug. 1992, pp. 1264–67. Pubmed, doi:10.1126/science.1325672.
Pitcher JA, Inglese J, Higgins JB, Arriza JL, Casey PJ, Kim C, Benovic JL, Kwatra MM, Caron MG, Lefkowitz RJ. 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):1264–1267.
Journal cover image

Published In

Science

DOI

ISSN

0036-8075

Publication Date

August 28, 1992

Volume

257

Issue

5074

Start / End Page

1264 / 1267

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Virulence Factors, Bordetella
  • Time Factors
  • Rhodopsin
  • Recombinant Fusion Proteins
  • Receptors, Adrenergic, beta
  • Protein Processing, Post-Translational
  • Protein Kinases
  • Phosphorylation
  • Molecular Sequence Data