Role of reactive oxygen species as signal transducers in β2 adrenergic receptor mediated β‐arrestin signaling (662.2)

Abstract

Reactive oxygen species (ROS) have previously been linked to deleterious effects caused by oxidative stress as well as to inflammatory disorders, degenerative disorders and cancers. More recently, ROS have been recognized as important signaling molecules, and have been shown to be involved in G protein‐coupled receptor (GPCR) signal transduction. Our laboratory has previously shown that agonism of the prototypical GPCR, the β2 adrenergic receptor (β2AR), generates intracellular ROS and that β2AR‐associated G protein signaling is dependent on ROS. Here, we demonstrate that ROS are critical mediators of β2AR signaling to β‐arrestins. Using coimmunoprecipitation and BRET, we reveal that the physical interaction of β2AR and β‐arrestins are dependent on ROS. Furthermore, using phosphorylation of ERK1/2 as an endpoint for both G‐protein and β‐arrestin signaling, we demonstrate that ROS are required for both G protein and β‐arrestin dependent ERK1/2 phosphorylation. These results are presented in light of data, which demonstrate that β2AR agonism can lead to receptor S‐Sulfenation, a process that is dependent on ROS, and which suggests that ROS may serve a purposeful role in stabilizing β2AR in signal‐capable conformations.Grant Funding Source: Internal funding