Figure 2. The β2AR-ROS feedback loop is dependent upon cysteine redox activity.

Known or hypothesized mechanisms whereby β2AR agonism may induce NADPH oxidase-based ROS generation include β-arrestin scaffolding of Rac-1, c-Src, or ERK1/2, all of which are known to activate NOX. β2AR-mediated transactivation of EGFR via c-Src may also presumably activate NOX via PI3K activity, while activation of Gαs signaling following β2AR agonism can also facilitate ERK1/2 activity. Once generated by NOX, superoxide can be dismutated to H₂O₂, which can oxidize β2AR cysteine residues forming Cys-S-sulfenic acids, which are seemingly required to uphold β2AR function, including G protein-signaling and β-arrestin scaffolding.