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Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors.

Publication ,  Journal Article
Pippig, S; Andexinger, S; Daniel, K; Puzicha, M; Caron, MG; Lefkowitz, RJ; Lohse, MJ
Published in: J Biol Chem
February 15, 1993

Receptor-specific or homologous desensitization of beta 2-adrenergic receptors is thought to be effected via phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK), followed by binding of beta-arrestin. We have generated stably transfected Chinese hamster ovary cell lines overexpressing either of the two regulatory proteins and also expressing low or high levels of beta 2-adrenergic receptors (approximately 80 and approximately 600 fmol/mg of membrane protein). In these cells, we studied the process of desensitization induced by the beta-adrenergic receptor agonist isoproterenol. In cells expressing high levels of beta 2-adrenergic receptors, desensitization to high concentrations of isoproterenol (previously shown to be mediated by both beta ARK and protein kinase A) amounted to approximately 50% in control cells, approximately 80% in beta ARK-overexpressing cells, and approximately 90% in beta-arrestin-overexpressing cells. In cells expressing low levels of beta 2-adrenergic receptors, these values were approximately 50, approximately 60, and approximately 60%, respectively. Desensitization to low concentrations of isoproterenol (previously shown to be essentially protein kinase A-mediated and not receptor-specific, i.e. heterologous) was not affected by overexpression of either beta ARK or beta-arrestin. These data suggest that in cells expressing high levels of beta 2-adrenergic receptors, beta-arrestin and beta ARK become limiting for homologous receptor desensitization. They provide further support for the involvement of these two proteins in the regulation of beta 2-adrenergic receptor function.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

February 15, 1993

Volume

268

Issue

5

Start / End Page

3201 / 3208

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Adrenergic Receptor Kinases
  • Transfection
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Pindolol
  • Phosphorus Radioisotopes
  • Peptides
  • Molecular Sequence Data
  • Magnesium Chloride
 

Citation

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Pippig, S., Andexinger, S., Daniel, K., Puzicha, M., Caron, M. G., Lefkowitz, R. J., & Lohse, M. J. (1993). Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors. J Biol Chem, 268(5), 3201–3208.
Pippig, S., S. Andexinger, K. Daniel, M. Puzicha, M. G. Caron, R. J. Lefkowitz, and M. J. Lohse. “Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors.J Biol Chem 268, no. 5 (February 15, 1993): 3201–8.
Pippig S, Andexinger S, Daniel K, Puzicha M, Caron MG, Lefkowitz RJ, et al. Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors. J Biol Chem. 1993 Feb 15;268(5):3201–8.
Pippig S, Andexinger S, Daniel K, Puzicha M, Caron MG, Lefkowitz RJ, Lohse MJ. Overexpression of beta-arrestin and beta-adrenergic receptor kinase augment desensitization of beta 2-adrenergic receptors. J Biol Chem. 1993 Feb 15;268(5):3201–3208.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

February 15, 1993

Volume

268

Issue

5

Start / End Page

3201 / 3208

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Adrenergic Receptor Kinases
  • Transfection
  • Receptors, Adrenergic, beta
  • Protein Kinases
  • Pindolol
  • Phosphorus Radioisotopes
  • Peptides
  • Molecular Sequence Data
  • Magnesium Chloride