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GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation.

Publication ,  Journal Article
Hu, LA; Chen, W; Martin, NP; Whalen, EJ; Premont, RT; Lefkowitz, RJ
Published in: J Biol Chem
July 11, 2003

Beta1-adrenergic receptors, expressed at high levels in the human heart, have a carboxyl-terminal ESKV motif that can directly interact with PDZ domain-containing proteins. Using the beta1-adrenergic receptor carboxyl terminus as bait, we identified the novel beta1-adrenergic receptor-binding partner GIPC in a yeast two-hybrid screen of a human heart cDNA library. Here we demonstrate that the PDZ domain-containing protein, GIPC, co-immunoprecipitates with the beta1-adrenergic receptor in COS-7 cells. Essential for this interaction is the Ser residue of the beta1-adrenergic receptor carboxyl-terminal ESKV motif. Our data also demonstrate that beta1-adrenergic receptor stimulation activates the mitogen-activated protein kinase, ERK1/2. beta1-adrenergic receptor-mediated ERK1/2 activation was inhibited by pertussis toxin, implicating Gi, and was substantially decreased by the expression of GIPC. Expression of GIPC had no observable effect on beta1-adrenergic receptor sequestration or receptor-mediated cAMP accumulation. This GIPC effect was specific for the beta1-adrenergic receptor and was dependent on an intact PDZ binding motif. These data suggest that GIPC can regulate beta1-adrenergic receptor-stimulated, Gi-mediated, ERK activation while having no effect on receptor internalization or Gs-mediated cAMP signaling.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 11, 2003

Volume

278

Issue

28

Start / End Page

26295 / 26301

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Transfection
  • Time Factors
  • Signal Transduction
  • Serine
  • Receptors, Adrenergic, beta-1
  • Protein Structure, Tertiary
  • Protein Binding
  • Precipitin Tests
  • Plasmids
 

Citation

APA
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Hu, L. A., Chen, W., Martin, N. P., Whalen, E. J., Premont, R. T., & Lefkowitz, R. J. (2003). GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation. J Biol Chem, 278(28), 26295–26301. https://doi.org/10.1074/jbc.M212352200
Hu, Liaoyuan A., Wei Chen, Negin P. Martin, Erin J. Whalen, Richard T. Premont, and Robert J. Lefkowitz. “GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation.J Biol Chem 278, no. 28 (July 11, 2003): 26295–301. https://doi.org/10.1074/jbc.M212352200.
Hu LA, Chen W, Martin NP, Whalen EJ, Premont RT, Lefkowitz RJ. GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation. J Biol Chem. 2003 Jul 11;278(28):26295–301.
Hu, Liaoyuan A., et al. “GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation.J Biol Chem, vol. 278, no. 28, July 2003, pp. 26295–301. Pubmed, doi:10.1074/jbc.M212352200.
Hu LA, Chen W, Martin NP, Whalen EJ, Premont RT, Lefkowitz RJ. GIPC interacts with the beta1-adrenergic receptor and regulates beta1-adrenergic receptor-mediated ERK activation. J Biol Chem. 2003 Jul 11;278(28):26295–26301.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 11, 2003

Volume

278

Issue

28

Start / End Page

26295 / 26301

Location

United States

Related Subject Headings

  • Two-Hybrid System Techniques
  • Transfection
  • Time Factors
  • Signal Transduction
  • Serine
  • Receptors, Adrenergic, beta-1
  • Protein Structure, Tertiary
  • Protein Binding
  • Precipitin Tests
  • Plasmids