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G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95.

Publication ,  Journal Article
Hu, LA; Chen, W; Premont, RT; Cong, M; Lefkowitz, RJ
Published in: J Biol Chem
January 11, 2002

We previously reported that the beta(1)-adrenergic receptor (beta(1)AR) associates with PSD-95 through a PDZ domain-mediated interaction, by which PSD-95 modulates beta(1)AR function and facilitates the physical association of beta(1)AR with other synaptic proteins such as N-methyl-d-aspartate receptors. Here we demonstrate that beta(1)AR association with PSD-95 is regulated by G protein-coupled receptor kinase 5 (GRK5). When beta(1)AR and PSD-95 were coexpressed with either GRK2 or GRK5 in COS-7 cells, GRK5 alone dramatically decreased the association of beta(1)AR with PSD-95, although GRK2 and GRK5 both could be co-immunoprecipitated with beta(1)AR and both could enhance receptor phosphorylation in vivo. Increasing expression of GRK5 in the cells led to further decreased beta(1)AR association with PSD-95. Stimulation with the beta(1)AR agonist isoproterenol further decreased PSD-95 binding to beta(1)AR. In addition, GRK5 protein kinase activity was required for this regulatory effect since a kinase-inactive GRK5 mutant had no effect on PSD-95 binding to beta(1)AR. Moreover, the regulatory effect of GRK5 on beta(1)AR association with PSD-95 was observed only when GRK5 was expressed together with the receptor, but not when GRK5 was coexpressed with PSD-95. Thus, we propose that GRK5 regulates beta(1)AR association with PSD-95 through phosphorylation of beta(1)AR. Regulation of protein association through receptor phosphorylation may be a general mechanism used by G protein-coupled receptors that associate via PDZ domain-mediated protein/protein interactions.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 11, 2002

Volume

277

Issue

2

Start / End Page

1607 / 1613

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Adrenergic Receptor Kinases
  • Transfection
  • Recombinant Fusion Proteins
  • Receptors, Adrenergic, beta-1
  • Protein Structure, Tertiary
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Phosphorylation
  • Nerve Tissue Proteins
 

Citation

APA
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ICMJE
MLA
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Hu, L. A., Chen, W., Premont, R. T., Cong, M., & Lefkowitz, R. J. (2002). G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95. J Biol Chem, 277(2), 1607–1613. https://doi.org/10.1074/jbc.M107297200
Hu, Liaoyuan A., Wei Chen, Richard T. Premont, Mei Cong, and Robert J. Lefkowitz. “G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95.J Biol Chem 277, no. 2 (January 11, 2002): 1607–13. https://doi.org/10.1074/jbc.M107297200.
Hu LA, Chen W, Premont RT, Cong M, Lefkowitz RJ. G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95. J Biol Chem. 2002 Jan 11;277(2):1607–13.
Hu, Liaoyuan A., et al. “G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95.J Biol Chem, vol. 277, no. 2, Jan. 2002, pp. 1607–13. Pubmed, doi:10.1074/jbc.M107297200.
Hu LA, Chen W, Premont RT, Cong M, Lefkowitz RJ. G protein-coupled receptor kinase 5 regulates beta 1-adrenergic receptor association with PSD-95. J Biol Chem. 2002 Jan 11;277(2):1607–1613.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 11, 2002

Volume

277

Issue

2

Start / End Page

1607 / 1613

Location

United States

Related Subject Headings

  • beta-Arrestins
  • beta-Adrenergic Receptor Kinases
  • Transfection
  • Recombinant Fusion Proteins
  • Receptors, Adrenergic, beta-1
  • Protein Structure, Tertiary
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Phosphorylation
  • Nerve Tissue Proteins