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

► We find β-arrestin-1 interacts with Gαs but not Gαi or Gαo. ► β-Arrestin-1 binds to Gαs in a rapid kinetic mode. ► β-Arrestin-1 promotes the binding and release of GTPγS from Gαs in vitro. ► The interaction deficient mutant β-arrestin-1 L33K has no detectable effects on the Gαs function.