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Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection.

Publication ,  Journal Article
Noma, T; Lemaire, A; Naga Prasad, SV; Barki-Harrington, L; Tilley, DG; Chen, J; Le Corvoisier, P; Violin, JD; Wei, H; Lefkowitz, RJ; Rockman, HA
Published in: J Clin Invest
September 2007

Deleterious effects on the heart from chronic stimulation of beta-adrenergic receptors (betaARs), members of the 7 transmembrane receptor family, have classically been shown to result from Gs-dependent adenylyl cyclase activation. Here, we identify a new signaling mechanism using both in vitro and in vivo systems whereby beta-arrestins mediate beta1AR signaling to the EGFR. This beta-arrestin-dependent transactivation of the EGFR, which is independent of G protein activation, requires the G protein-coupled receptor kinases 5 and 6. In mice undergoing chronic sympathetic stimulation, this novel signaling pathway is shown to promote activation of cardioprotective pathways that counteract the effects of catecholamine toxicity. These findings suggest that drugs that act as classical antagonists for G protein signaling, but also stimulate signaling via beta-arrestin-mediated cytoprotective pathways, would represent a novel class of agents that could be developed for multiple members of the 7 transmembrane receptor family.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

September 2007

Volume

117

Issue

9

Start / End Page

2445 / 2458

Location

United States

Related Subject Headings

  • beta-Arrestins
  • Transcriptional Activation
  • Signal Transduction
  • Receptors, Adrenergic, beta-1
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Phosphorylation
  • Myocardium
  • Mutation
  • Mice, Transgenic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Noma, T., Lemaire, A., Naga Prasad, S. V., Barki-Harrington, L., Tilley, D. G., Chen, J., … Rockman, H. A. (2007). Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection. J Clin Invest, 117(9), 2445–2458. https://doi.org/10.1172/JCI31901
Noma, Takahisa, Anthony Lemaire, Sathyamangla V. Naga Prasad, Liza Barki-Harrington, Douglas G. Tilley, Juhsien Chen, Philippe Le Corvoisier, et al. “Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection.J Clin Invest 117, no. 9 (September 2007): 2445–58. https://doi.org/10.1172/JCI31901.
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, et al. Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection. J Clin Invest. 2007 Sep;117(9):2445–58.
Noma, Takahisa, et al. “Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection.J Clin Invest, vol. 117, no. 9, Sept. 2007, pp. 2445–58. Pubmed, doi:10.1172/JCI31901.
Noma T, Lemaire A, Naga Prasad SV, Barki-Harrington L, Tilley DG, Chen J, Le Corvoisier P, Violin JD, Wei H, Lefkowitz RJ, Rockman HA. Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection. J Clin Invest. 2007 Sep;117(9):2445–2458.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

September 2007

Volume

117

Issue

9

Start / End Page

2445 / 2458

Location

United States

Related Subject Headings

  • beta-Arrestins
  • Transcriptional Activation
  • Signal Transduction
  • Receptors, Adrenergic, beta-1
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Phosphorylation
  • Myocardium
  • Mutation
  • Mice, Transgenic