Reactive oxygen species (ROS) have become recognized for their role as second messengers in a multitude of physiologic responses. Emerging evidence points to the importance of the NADPH oxidase family of ROS-producing enzymes in mediating redox-sensitive signal transduction. However, a clear paradox exists between the specificity required for signaling and the nature of ROS as both diffusible and highly reactive molecules. We seek to understand the targets and compartmentalization of the NADPH oxidase signaling to determine how NADPH oxidase-derived ROS fit into established signaling paradigms. Herein we review recent data that link cellular NADPH oxidase enzymes to ROS signaling, with a particular focus on the mechanism(s) involved in achieving signaling specificity.
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