The phagocyte NADPH oxidase is dormant in resting cells but becomes activated 
during phagocytosis to produce superoxide, a precursor of microbicidal oxidants, 
thereby playing a crucial role in host defence. The catalytic core of this 
enzyme comprises the two membranous subunits gp91phox/Nox2 and p22phox. The 
oxidase activation requires the small GTPase Rac and the SH3 domain-containing 
proteins p47phox and p67phox; they normally exist in the cytoplasm and 
translocate upon cell stimulation to the membrane. The translocation depends on 
a stimulus-induced conformational change of p47phox, which leads to the SH3 
domain-mediated interaction with p22phox, a binding required for the 
gp91phox/Nox2-dependent superoxide production. Activation of Nox1, an oxidase 
that is likely involved in host defence at the colon, requires novel proteins 
homologous to p47phox and p67phox, designated Noxo1 and Noxa1, respectively. 
Noxo1 and Noxa1, both expressed abundantly in the colon, are capable of 
constitutively activating Nox1. The constitutive activation may be due to the 
property of Noxo1: in contrast with p47phox, Noxo1 seems to normally associate 
with p22phox, which is required for the Nox1 activation. We will also describe 
the mechanism underlying regulation of the third oxidase Nox3, which exits in 
fetal kidney and inner ears.