INTERACTION OF RAC WITH P67(PHOX) AND REGULATION OF PHAGOCYTIC NADPH OXIDASE ACTIVITY

Rho and Rac, two members of the Ras superfamily of guanosine triphosph ate (GIP)-binding proteins, regulate a variety of signal transduction pathways in eukaryotic cells. Upon stimulation of phagocytic cells, Ra c enhances the activity of the enzyme nicotinamide adenine dinucleotid e phosphate (reduced) (NADPH) oxidase, resulting in the production of superoxide radicals. Activation of the NADPH oxidase requires the asse mbly of a multimolecular complex at the plasma membrane consisting of two integral membrane proteins, gp91(phox) and p2l(phox), and two cyto solic proteins, p67(phox) and p47(phox). Rac1 interacted directly with p67(phox) in GTP-dependent manner. Modified forms of Rac with mutatio ns in the effector site did not stimulate oxidase activity or bind to p67(phox). Thus, p67(phox) appears to be the Rac effector protein in t he NADPH oxidase complex.