p40phox participates in the activation of NADPH oxidase by increasing the affinity of p47phox for flavocytochrome b558

• Published in: Biochemical journal 2000-07, Vol.349 (1), p.113-117
• Main Author: CROSS, Andrew R.
• Format: Article
• Language: eng ; jpn
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3490113

NADPH oxidase is one of the major components of the innate immune system and is used by phagocytes to generate microbicidal reactive oxygen species. Activation of the enzyme requires the participation of a minimum of five proteins, p22phox, gp91phox (together forming flavocytochrome b558), p47phox, p67phox and the GTP-binding protein, Rac2. A sixth protein, p40phox, has been implicated in the control of the activity of NADPH oxidase principally 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 positive and negative influences on oxidase activity having being reported. Data are presented here using the cell-free system for NADPH oxidase activation that shows that p40phox can function to promote oxidase activation by increasing the affinity of p47phox for the enzyme approx. 3-fold.