Jpn. J. Infect. Dis., 57, S24-S25, 2004
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Molecular Mechanism Underlying Activation
of Superoxide-Producing NADPH Oxidases: Roles for Their Regulatory
Proteins
Hideki Sumimoto*, Noriko Ueno, Tomoko Yamasaki, Masahiko
Taura and Ryu Takeya
Medical Institute of Bioregulation, Kyushu University, Fukuoka,
CREST of
Japan Science and Technology Agency, Saitama, Japan
*Corresponding author: hsumi@bioreg.kyushu-u.ac.jp
SUMMARY: 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.