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Phosphorylation of β-arrestin 2 at Thr(383) by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs.

Phosphorylation of β-arrestin 2 at Thr(383) by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs.
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Cassier E, Gallay N, Bourquard T, Claeysen S, Bockaert J, Crépieux P, Poupon A, Reiter E, Marin P, Vandermoere F,


Cassier E, Gallay N, Bourquard T, Claeysen S, Bockaert J, Crépieux P, Poupon A, Reiter E, Marin P, Vandermoere F, (click to view)

Cassier E, Gallay N, Bourquard T, Claeysen S, Bockaert J, Crépieux P, Poupon A, Reiter E, Marin P, Vandermoere F,

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eLife 2017 02 076() doi 10.7554/eLife.23777

Abstract

In addition to their role in desensitization and internalization of G protein-coupled receptors (GPCRs), β-arrestins are essential scaffolds linking GPCRs to Erk1/2 signaling. However, their role in GPCR-operated Erk1/2 activation differs between GPCRs and the underlying mechanism remains poorly characterized. Here, we show that activation of serotonin 5-HT2C receptors, which engage Erk1/2 pathway via a β-arrestin-dependent mechanism, promotes MEK-dependent β-arrestin 2 phosphorylation at Thr(383), a necessary step for Erk recruitment to the receptor/β-arrestin complex and Erk activation. Likewise, Thr(383) phosphorylation is involved in β-arrestin-dependent Erk1/2 stimulation elicited by other GPCRs such as β2-adrenergic, FSH and CXCR4 receptors, but does not affect the β-arrestin-independent Erk1/2 activation by 5-HT4 receptor. Collectively, these data show that β-arrestin 2 phosphorylation at Thr(383) underlies β-arrestin-dependent Erk1/2 activation by GPCRs.

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