Phagocyte NADPH oxidase p67-phox possesses a novel carboxylterminal binding site for the GTPases Rac2 and Cdc42.

Rac GTPases regulate activation of the phagocyte NADPH oxidase, a multi-component enzyme complex that produces superoxide in response to host infection. GTP-bound Rac binds to the cytosol protein p67-phox enabling it to participate in oxidase assembly. Details of this interaction are poorly understood. Previous studies showed that Rac/p67-phox binding is ...
GTP-dependent and that several Rac1 mutants lost the ability to activate the oxidase even though they still bound p67-phox. Using two hybrid and blot overlay binding methods, we identified a novel binding site in the p67-phox C-terminus that binds Rac1, Rac2, and Cdc42, a related GTPase which does not activate the oxidase. Binding was independent of the GDP/GTP state. We also showed that GTP-Cdc42 binds p67-phox N-terminus similar to GTP-Rac. Therefore, Rac binding to p67-phox is not synonymous with NADPH oxidase activation, and Rac probably participates in other steps of oxidase activation in addition to binding p67-phox.
Mesh Terms:
Binding Sites, Cell Cycle Proteins, Enzyme Activation, GTP Phosphohydrolases, GTP-Binding Proteins, Humans, NADPH Oxidase, Phagocytes, Phosphoproteins, Recombinant Proteins, Saccharomyces cerevisiae, cdc42 GTP-Binding Protein, rac GTP-Binding Proteins
Biochem. Biophys. Res. Commun.
Date: Jun. 18, 1998
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