β-Arrestin-1 directly interacts with Gαs and regulates its function.

β-Arrestins function to mediate G protein-coupled receptor (GPCR) desensitization and internalization and to initiate G protein independent signaling of GPCRs. Elucidating how β-arrestin and G protein signal pathways coordinate with each other is important to fully understand GPCR signaling. Here we report that β-arrestin-1 directly interacts with Gα(s). Purified β-arrestin-1 binds to Gα(s) in a rapid association and dissociation manner. β-Arrestin-1 promotes the binding and the release of GTPγS from Gα(s) in vitro. β-Arrestin-1 L33K mutant shows reduced interaction with Gα(s) and has no detectable effects on Gα(s) function. Our study thus reveals a direct crosstalk of β-arrestin-1 with Gα(s).