Reactive oxygen species are required for β2 adrenergic receptor–β-arrestin interactions and signaling to ERK1/2

摘要: Abstract The β2-adrenergic receptor (β2AR) is the prototypical member of heptahelical G protein-coupled (GPCR) superfamily and well-known to elicit biological effects through both protein-dependent protein-independent signaling cascades. Agonism β2AR has been described promote phosphorylation activation extracellular signal-regulated kinases (ERK1/2) via a G-protein/PKA pathway that transpires rapidly upon agonism, as well by distinct β-arrestin-mediated occurs at later time points. We have previously shown agonism promotes generation intracellular reactive oxygen species (ROS) β2AR-associated protein dependent on ROS formation. It also suggested β2AR-mediated recruitment β-arrestins. In this study, we confirm β-arrestin β2AR-induced generation, investigate ROS-dependency β-arrestin-linked signaling. HEK293 cells, coimmunoprecipitation BRET studies reveal are vital for physical interaction with partner proteins. Using ERK1/2 functional endpoint assess role in β2AR–β-arrestin signaling, our results show inhibition abrogates protein-mediated β2AR. Importantly, components were reversed exogenous administration ROS, suggesting critical oxidants stabilization Taken together, data signify serve purposeful roles stabilizing protein- cells.