Phosphorylation of β-arrestin2 at Thr383by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs.
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-HT2Creceptors, 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, Thr383phosphorylation 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-HT4receptor. Collectively, these data show that β-arrestin2 phosphorylation at Thr383underlies β-arrestin-dependent Erk1/2 activation by GPCRs.
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.|INSERM, U1191, Montpellier, France.|Université de Montpellier, Montpellier, France.
Elisabeth
E
Cassier
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France.|CNRS, UMR7247, Nouzilly, France.|Université François Rabelais, Tours, France.
Nathalie
N
Gallay
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France.|CNRS, UMR7247, Nouzilly, France.|Université François Rabelais, Tours, France.
Thomas
T
Bourquard
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.|INSERM, U1191, Montpellier, France.|Université de Montpellier, Montpellier, France.
Sylvie
S
Claeysen
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.|INSERM, U1191, Montpellier, France.|Université de Montpellier, Montpellier, France.
Joël
J
Bockaert
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France.|CNRS, UMR7247, Nouzilly, France.|Université François Rabelais, Tours, France.
Pascale
P
Crépieux
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France.|CNRS, UMR7247, Nouzilly, France.|Université François Rabelais, Tours, France.
Anne
A
Poupon
INRA, UMR85, Unité Physiologie de la Reproduction et des Comportements, Nouzilly, France.|CNRS, UMR7247, Nouzilly, France.|Université François Rabelais, Tours, France.
Eric
E
Reiter
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.|INSERM, U1191, Montpellier, France.|Université de Montpellier, Montpellier, France.
Philippe
0000-0002-5977-7274
P
Marin
CNRS, UMR-5203, Institut de Génomique Fonctionnelle, Montpellier, France.|INSERM, U1191, Montpellier, France.|Université de Montpellier, Montpellier, France.
Franck
F
Vandermoere
D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D000071560:beta-Arrestin 2 / Q000378:metabolism*
D043562:Receptors, G-Protein-Coupled; D011985:Receptors, Serotonin; D000071560:beta-Arrestin 2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases
Extracellular signal-regulated kinase; G protein-coupled receptor; cell biology; human; mass spectrometry; phosphorylation; rat; β-arrestin