Neutrophil cytosolic factor 4, 40kDa Adenovirus (Ad-p40Phox)

The superoxide-generating NADPH oxidase is present in phagocytes, neuroepithelial bodies, vascular smooth muscle cells and endothelial cells. It includes a membrane-bound flavocytochrome containing gp91-phox, Nox4 and p22-phox, and the cytosolic proteins, p40-phox, p47-phox and p67-phox. During activation of the NADPH oxidase, p47-phox and p67-phox migrate to the plasma membrane where they associate with the flavocytochrome cytochrome b558 to form the active enzyme complex. Mox1 is largely similar to gp91 and is involved in regulating NADPH oxidase activity in non-phagocytic cells. P40-phox interacts primarily with neutrophil cytosolic factor 2 (NCF2/p67-phox) to form a complex with neutrophil cytosolic factor 1 (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex then activates flavocytochrome b, the membrane-integrated catalytic core of the enzyme system. The PX domain of this protein can bind phospholipid products of the PI (3) kinase, which suggests its role in PI (3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity.