p40(phox) participates in the activation of NADPH oxidase by increasing the affinity of p47(phox) for flavocytochrome b(558)

NADPH oxidase is one of the major components of the innate immune system an d is used by phagocytes to generate microbicidal reactive oxygen species. A ctivation of the enzyme requires the participation of a minimum of five pro teins, D22(phox), gp91(phox) (together forming flavocytochrome b(558)), p47 (phox), p67(phox) and the GTP-binding protein, Rac2. A sixth protein, p40(p hox), has been implicated in the control of the activity of NADPH oxidase p rincipally based on its sequence homology to, and physical association with , other phox components, and also the observation that it is phosphorylated during neutrophil activation. However, to date its role in regulating the activity of the enzyme has remained obscure, with evidence for both positiv e and negative influences on oxidase activity having being reported. Data a re presented here using the cell-free system for NADPH oxidase activation t hat shows that p40(phox) can function to promote oxidase activation by incr easing the affinity of p37(phox) for the enzyme approx. 3-fold.