Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases

Yuichi Maehara, Kei Miyano, Hideki Sumimoto

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The membrane-bound NADPH oxidase in phagocytes, gp91phox (a.k.a. Nox2), produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. Although the C-terminal SH3 domain of p67phox is responsible for binding to p47phox, little is known about the role for the first (N-terminal) SH3 domain [SH3(N)]. Here we show that truncation of p67phox-SH3(N), but not substitution of arginine for the invariant residue Trp-277 in SH3(N), results in an impaired activation of gp91phox/Nox2. The impairment is overcome by higher expression of an SH3(N)-defective p67phox in cells, suggesting that SH3(N) primarily increases the affinity of p67phox for the oxidase complex. On the other hand, p67phox-SH3(N) is not involved in activation of Nox1 and Nox3, closely-related homologues of gp91phox/Nox2. Thus p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly.

Original languageEnglish
Pages (from-to)589-593
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume379
Issue number2
DOIs
Publication statusPublished - Feb 6 2009

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src Homology Domains
NADPH Oxidase
Superoxides
Chemical activation
Oxidoreductases
Phagocytes
neutrophil cytosol factor 67K
Oxidants
Arginine
Substitution reactions
Membranes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases. / Maehara, Yuichi; Miyano, Kei; Sumimoto, Hideki.

In: Biochemical and Biophysical Research Communications, Vol. 379, No. 2, 06.02.2009, p. 589-593.

Research output: Contribution to journalArticle

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