Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 24, Issue 10, Pages 4384-4394Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.24.10.4384-4394.2004
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The generation of reactive oxygen species (ROS) in cells stimulated with growth factors requires the activation of phosphatidylinositol 3-kinase (PI3K) and the Rac protein. We report here that the COOH-terminal region of Nox1, a protein related to gp91(phox) (Nox2) of phagocytic cells, is constitutively associated with PPix, a guanine nucleotide exchange factor for Rac. Both growth factor-induced ROS production and Rac1 activation were completely blocked in cells depleted of betaPix by RNA interference. Rac1 was also shown to bind to the COOH-terminal region of Nox1 in a growth factor-dependent manner. Moreover, the depletion of Nox1 by RNA interference inhibited growth factor-induced ROS generation. These results suggest that ROS production in growth factor-stimulated cells is mediated by the sequential activation of PI3K, betaPix, and Rac1, which then binds to Nox1 to stimulate its NADPH oxidase activity.
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