Molecular mechanism underlying activation of superoxide-producing NADPH oxidases: Roles for their regulatory proteins

Hideki Sumimoto, Noriko Yamamoto, Tomoko Yamasaki, Masahiko Taura, Ryu Takeya

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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 Rae 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 gp96phox /Nox2-dependent super-oxide 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.

Original languageEnglish
JournalJapanese Journal of Infectious Diseases
Volume57
Issue number5
Publication statusPublished - Oct 2004

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NADPH Oxidase
Superoxides
Oxidoreductases
src Homology Domains
Colon
Proteins
Monomeric GTP-Binding Proteins
Inner Ear
Phagocytes
Phagocytosis
Oxidants
Oxides
Catalytic Domain
Cytoplasm
Kidney
Membranes
Enzymes
neutrophil cytosol factor 67K

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Molecular mechanism underlying activation of superoxide-producing NADPH oxidases : Roles for their regulatory proteins. / Sumimoto, Hideki; Yamamoto, Noriko; Yamasaki, Tomoko; Taura, Masahiko; Takeya, Ryu.

In: Japanese Journal of Infectious Diseases, Vol. 57, No. 5, 10.2004.

Research output: Contribution to journalArticle

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