Résumé
In addition to their role in desensitization and internalization of G protein-coupled receptors (GPCRs), b-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-HT 2C receptors, which engage Erk1/2 pathway via a b-arrestin-dependent mechanism, promotes MEK-dependent b-arrestin2 phosphorylation at Thr 383 , a necessary step for Erk recruitment to the receptor/b-arrestin complex and Erk activation. Likewise, Thr 383 phosphorylation is involved in b-arrestin-dependent Erk1/2 stimulation elicited by other GPCRs such as b 2-adrenergic, FSH and CXCR4 receptors, but does not affect the b-arrestin-independent Erk1/2 activation by 5-HT 4 receptor. Collectively, these data show that b-arrestin2 phosphorylation at Thr 383 underlies b-arrestin-dependent Erk1/2 activation by GPCRs.