Phosphorylation of β-arrestin 2 at Thr383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs
- CNRS, UMR-5203, Institut de Génomique Fonctionnelle, France
- INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, France
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 Thr383, a necessary step for Erk recruitment to the receptor/β-arrestin complex and Erk activation. Likewise, Thr383 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 Thr383 underlies β-arrestin-dependent Erk1/2 activation by GPCRs.
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Funding
Fondation pour la Recherche Médicale (Contract Equipe FRM 2009)
- Elisabeth Cassier
- Sylvie Claeysen
- Joël Bockaert
- Philippe Marin
- Franck Vandermoere
Agence Nationale de la Recherche (Contract ANR-2011-1619 01)
- Elisabeth Cassier
- Nathalie Gallay
- Thomas Bourquard
- Sylvie Claeysen
- Joël Bockaert
- Pascale Crépieux
- Anne Poupon
- Eric Reiter
- Philippe Marin
- Franck Vandermoere
Centre National de la Recherche Scientifique
- Elisabeth Cassier
- Sylvie Claeysen
- Joël Bockaert
- Philippe Marin
- Franck Vandermoere
Institut National de la Santé et de la Recherche Médicale
- Elisabeth Cassier
- Sylvie Claeysen
- Joël Bockaert
- Philippe Marin
- Franck Vandermoere
Université de Montpellier
- Elisabeth Cassier
- Sylvie Claeysen
- Joël Bockaert
- Philippe Marin
- Franck Vandermoere
Institut National de la Recherche Agronomique
- Nathalie Gallay
- Thomas Bourquard
- Pascale Crépieux
- Anne Poupon
- Eric Reiter
Université François-Rabelais
- Nathalie Gallay
- Thomas Bourquard
- Pascale Crépieux
- Anne Poupon
- Eric Reiter
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Cassier et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Phosphorylation of β-arrestin 2 at Thr383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs
eLife 6:e23777.
https://doi.org/10.7554/eLife.23777
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