Antagonistic cross-talk between Rac and Cdc42 GTPases regulates generation of reactive oxygen species.

摘要: Cross-talk between Rho GTPase family members (Rho, Rac, and Cdc42) plays important roles in modulating coordinating downstream cellular responses resulting from signaling. The NADPH oxidase of phagocytes nonphagocytic cells is a Rac GTPase-regulated system that generates reactive oxygen species (ROS) for the purposes innate immunity intracellular We recently demonstrated activation involves sequential interactions flavocytochrome b558 p67phox components to regulate electron transfer molecular oxygen. Here we identify an antagonistic interaction closely related Cdc42 at level regulates formation ROS. unable stimulate ROS by oxidase, but Cdc42, like Rac1 Rac2, was able specifically bind b558in vitro. acted as competitive inhibitor Rac1- Rac2-mediated recombinant cell-free system. Inhibition dependent on insert domain not Switch I region. Transient expression Cdc42Q61L inhibited induced constitutively active oxidase-expressing Cos7 cell line. activity transduction Cdc42-binding Wiscott-Aldrich syndrome protein into human neutrophils resulted enhanced fMetLeuPhe-induced oxidative response, consistent with inhibitory cross-talk activated neutrophils. propose here novel antagonism GTPases Nox proteins modulates generation used host defense, signaling, transformation.