Signaling Without G Proteins

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Science  25 Jun 2010:
Vol. 328, Issue 5986, pp. 1613
DOI: 10.1126/science.328.5986.1613-c

The angiotensin II receptor is a key regulator of blood pressure and other physiological processes. Binding of its ligand activates an associated heterotrimeric guanine nucleotide–binding protein (G protein). Rakesh et al. describe a different signal emitted by this receptor in the mouse heart when it responds to a mechanical stimulus. Usually, the protein β-arrestin acts to limit signaling by G protein–coupled receptors, but it can also promote signaling cascades that are independent of G proteins. Stretching the mouse heart by inflating a balloon within the left ventricle triggered receptor signaling that was independent of its associated G protein but that required β-arrestin 2 and the protein kinases that stimulate the association of β-arrestin 2 with the receptor. Such β-arrestin–dependent signaling by the angiotensin II receptor may turn on protective mechanisms when the heart is under stress. Indeed, the hearts of mice lacking β-arrestin 2 or the angiotensin II receptor showed reduced signaling and increased cell death in response to mechanical stretch.

Sci. Signal. 3, ra46 (2010).

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