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  • The EMBO Journal (2002) 21, 6312 - 6320
  • doi:10.1093/emboj/cdf642

The adaptor protein p40phox as a positive regulator of the superoxide-producing phagocyte oxidase

Futoshi Kuribayashi1,2, Hiroyuki Nunoi3, Kaori Wakamatsu4,5, Shohko Tsunawaki6, Kazuki Sato7, Takashi Ito8 and Hideki Sumimoto1,2,5

  1. Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  2. Department of Molecular and Structural Biology, Kyushu University Graduate School of Medical Science, Fukuoka 812-8582, Japan
  3. Department of Pediatrics, Miyazaki Medical College, Miyazaki 889-1692, Japan
  4. Department of Biochemical and Chemical Engineering, Faculty of Engineering, Gunma University, Kiryu 376-8515, Japan
  5. CREST JST (Japan Science and Technology), Tokyo 154-8509, Japan
  6. Department of Infectious Disease, National Children's Medical Research Center, Tokyo 154-8509, Japan
  7. Department of Environmental Science, Faculty of Human Environmental Science, Fukuoka Women's University, Fukuoka 813-8529 Japan
  8. Division of Genome Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan

Correspondence to:

Hideki Sumimoto, E-mail: hsumi@bioreg.kyushu-u.ac.jp

Received 16 May 2002; Accepted 15 October 2002; Revised 27 September 2002

Activation of the superoxide-producing phagocyte NADPH oxidase, crucial in host defense, requires the cytosolic proteins p67phox and p47phox. They translocate to the membrane upon cell stimulation and activate flavocytochrome b558, the membrane-integrated catalytic core of this enzyme system. The activators p67phox and p47phox form a ternary complex together with p40phox, an adaptor protein with unknown function, comprising the PX/PB2, SH3 and PC motif- containing domains: p40phox associates with p67phox via binding of the p40phox PC motif to the p67phox PB1 domain, while p47phox directly interacts with p67phox but not with p40phox. Here we show that p40phox enhances membrane translocation of p67phox and p47phox in stimulated cells, which leads to facilitated production of superoxide. The enhancement cannot be elicited by a mutant p40phox carrying the D289A substitution in PC or a p67phox with the K355A substitution in PB1, each being defective in binding to its respective partner. Thus p40phox participates in activation of the phagocyte oxidase by regulating membrane recruitment of p67phox and p47phox via the PB1–PC interaction with p67phox.

  • Keywords:

    • NADPH oxidase,
    • p40phox,
    • p67phox,
    • PB1 domain,
    • PC motif