Regulation of NADPH oxidases: the role of Rac proteins.

The role for reactive oxygen species (ROS) in cellular (patho)physiology, in particular in signal transduction, is increasingly recognized. The family of NADPH oxidases (NOXes) plays an important role in the production of ROS in response to receptor agonists such as growth factors or inflammatory cytokines that signal through the Rho-like small GTPases Rac1 or Rac2. The phagocyte oxidase (gp91phox/NOX2) is the best characterized family member, and its mode of activation is relatively well understood. Recent work has uncovered novel and increasingly complex modes of control of the NOX2-related proteins. Some of these, including NOX2, have been implicated in various aspects of (cardio)vascular disease, including vascular smooth muscle and endothelial cell hypertrophy and proliferation, inflammation, and atherosclerosis. This review focuses on the role of the Rac1 and Rac2 GTPases in the activation of the various NOX family members.