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beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress.

Publication ,  Journal Article
Rakesh, K; Yoo, B; Kim, I-M; Salazar, N; Kim, K-S; Rockman, HA
Published in: Sci Signal
June 8, 2010

beta-Arrestins, which were originally characterized as terminators of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) signaling, also act as important signal transducers. An emerging concept in GPCR signaling is beta-arrestin-biased agonism, in which specific ligand-activated GPCR conformational states selectively signal through beta-arrestins, rather than through G proteins. Here, we show that mechanical stretch induced beta-arrestin-biased signaling downstream of angiotensin II type I receptors (AT1Rs) in the absence of ligand or G protein activation. Mechanical stretch triggered an AT1R-mediated conformational change in beta-arrestin similar to that induced by a beta-arrestin-biased ligand to selectively stimulate receptor signaling in the absence of detectable G protein activation. Hearts from mice lacking beta-arrestin or AT1Rs failed to induce responses to mechanical stretch, as shown by blunted extracellular signal-regulated kinase and Akt activation, impaired transactivation of the epidermal growth factor receptor, and enhanced myocyte apoptosis. These data show that the heart responds to acute increases in mechanical stress by activating beta-arrestin-mediated cell survival signals.

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Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

June 8, 2010

Volume

3

Issue

125

Start / End Page

ra46

Location

United States

Related Subject Headings

  • beta-Arrestins
  • Stress, Mechanical
  • Receptors, Angiotensin
  • Protein Transport
  • Protein Conformation
  • Mice
  • Humans
  • Arrestins
  • Animals
  • 3101 Biochemistry and cell biology
 

Citation

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Rakesh, K., Yoo, B., Kim, I.-M., Salazar, N., Kim, K.-S., & Rockman, H. A. (2010). beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci Signal, 3(125), ra46. https://doi.org/10.1126/scisignal.2000769
Rakesh, Kriti, ByungSu Yoo, Il-Man Kim, Natasha Salazar, Ki-Seok Kim, and Howard A. Rockman. “beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress.Sci Signal 3, no. 125 (June 8, 2010): ra46. https://doi.org/10.1126/scisignal.2000769.
Rakesh K, Yoo B, Kim I-M, Salazar N, Kim K-S, Rockman HA. beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci Signal. 2010 Jun 8;3(125):ra46.
Rakesh, Kriti, et al. “beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress.Sci Signal, vol. 3, no. 125, June 2010, p. ra46. Pubmed, doi:10.1126/scisignal.2000769.
Rakesh K, Yoo B, Kim I-M, Salazar N, Kim K-S, Rockman HA. beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci Signal. 2010 Jun 8;3(125):ra46.

Published In

Sci Signal

DOI

EISSN

1937-9145

Publication Date

June 8, 2010

Volume

3

Issue

125

Start / End Page

ra46

Location

United States

Related Subject Headings

  • beta-Arrestins
  • Stress, Mechanical
  • Receptors, Angiotensin
  • Protein Transport
  • Protein Conformation
  • Mice
  • Humans
  • Arrestins
  • Animals
  • 3101 Biochemistry and cell biology