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Phosphorylation of β-arrestin 2 at Thr383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs

  1. Elisabeth Cassier
  2. Nathalie Gallay
  3. Thomas Bourquard
  4. Sylvie Claeysen
  5. Joël Bockaert
  6. Pascale Crépieux
  7. Anne Poupon
  8. Eric Reiter
  9. Philippe Marin  Is a corresponding author
  10. Franck Vandermoere  Is a corresponding author
  1. CNRS, UMR-5203, Institut de Génomique Fonctionnelle, France
  2. INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, France
Research Article
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Cite this article as: eLife 2017;6:e23777 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 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.

Article and author information

Author details

  1. Elisabeth Cassier

    CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Nathalie Gallay

    INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas Bourquard

    INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Sylvie Claeysen

    CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Joël Bockaert

    CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Pascale Crépieux

    INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Anne Poupon

    INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Eric Reiter

    INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Philippe Marin

    CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France
    For correspondence
    philippe.marin@igf.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5977-7274
  10. Franck Vandermoere

    CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France
    For correspondence
    franck.vandermoere@igf.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.

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.

Reviewing Editor

  1. Roger J Davis, University of Massachusetts Medical School, United States

Publication history

  1. Received: November 29, 2016
  2. Accepted: February 6, 2017
  3. Accepted Manuscript published: February 7, 2017 (version 1)
  4. Version of Record published: February 24, 2017 (version 2)

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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