Phosphorylation of b-arrestin2 at Thr 383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs

11Citations
Citations of this article
37Readers
Mendeley users who have this article in their library.

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-arrestin2 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-arrestin2 phosphorylation at Thr383 underlies β-arrestin-dependent Erk1/2 activation by GPCRs.

Cite

CITATION STYLE

APA

Cassier, E., Gallay, N., Bourquard, T., Claeysen, S., Bockaert, J., Crépieux, P., … Vandermoere, F. (2017). Phosphorylation of b-arrestin2 at Thr 383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs. ELife, 6. https://doi.org/10.7554/eLife.23777

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free