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Sci. Signal., 8 June 2010
Vol. 3, Issue 125, p. ra46
[DOI: 10.1126/scisignal.2000769]


Editor's Summary

An Arrestin Stretch
Activation of G protein–coupled receptors (GPCRs) can selectively trigger distinct signaling cascades through a process known as biased agonism. Mechanical stress has been linked to activation of the angiotensin type I receptor (AT1R) in a manner that does not require its ligand (angiotensin II). Rakesh et al. found that, in cells and ex vivo heart preparations, mechanical stress activated a signaling pathway that required neither angiotensin II nor G proteins. Instead, β-arrestin was recruited to AT1R, the complex was internalized, and β-arrestin activated an antiapoptotic signaling pathway through extracellular signal–regulated kinase (ERK) and Akt. Treating mice with the angiotensin receptor blocker losartan led to increased cardiomyocyte apoptosis, leading the authors to suggest that these drugs may block β-arrestin–mediated protective signaling in response to mechanical stress.

Citation: K. Rakesh, B. Yoo, I.-M. Kim, N. Salazar, K.-S. Kim, H. A. Rockman, β-Arrestin–Biased Agonism of the Angiotensin Receptor Induced by Mechanical Stress. Sci. Signal. 3, ra46 (2010).

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