Mechanism for interaction between Nox2/gp91^<phox>and p22^<phox>: two membrane proteins of the phagocyte NADPH oxidase

• Project/Area Number: 23790338
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: MIYANO Kei 九州大学, 医学研究院, 特任助教 (60444783)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: NADPHオキシダーゼ / 活性酸素 / Nox2/gp91^<phox> / 膜タンパク質 / Nox

Research Abstract

The phagocyte NADPH oxidase, dormant in resting cells, is activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. The catalytic core of the phagocyte oxidase is Nox2/gp91^<phox>, a membrane-spaning protein that forms a stable heterodimer with p22^<phox>. In this study, I found thatboth N-and C-terminal regions play a crucial role in Nox binding to p22^<phox>.Furthermore, I found that the addition of a specific region of nonphagocytic Nox (Nox5) to Nox2 leads to a large amount of Nox2 protein expression.

Research Products

• [Journal Article] Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activatorDOCK2 (2012)
  • Author(s): Nishikimi A, Uruno T, Duan X, Cao Q, Okamura Y, Saitoh T, Saitoh N, Sakaoka S, Du Y, Suenaga A, Kukimoto-Niino M, Miyano K, Gotoh K, Okabe T, Sanematsu F, Tanaka Y, Sumimoto H., Honma T, Yokoyama S, Nagano T, Kohda D, Kanai M, and Fukui Y
  • Journal Title: Chem. Biol Volume: 19 Issue: 4 Pages: 488-497
  • DOI: 10.1016/j.chembiol.2012.03.008
  • Peer Reviewed
• [Journal Article] Atypical membrane-embedded p47^<phox> PI(3,4)P_2 binding site on PX domain revealed by NMR (2012)
  • Author(s): Stampoulis P, Ueda T, Matsumoto M, Terasawa H, Miyano K, Sumimoto H, and Shimada I
  • Journal Title: J. Biol. Chem Volume: 287 Issue: 21 Pages: 17848-17859
  • DOI: 10.1074/jbc.m111.332874
  • Peer Reviewed
• [Journal Article] Assessment of the role for Rho family GTPases in NADPHoxidase activation (2012)
  • Author(s): Miyano K, Sumimoto H
  • Journal Title: Methods Mol. Biol Volume: 827 Pages: 195-212
  • DOI: 10.1007/978-1-61779-442-1_14
  • ISBN: 9781617794414, 9781617794421
  • Peer Reviewed
• [Journal Article] Selectively induced apoptosis in human neutrophils in the presence of oxidative phenoxazines, 2-amino-4, 4α-dihydryo-4α-7H-phenoxazine-3-one and 2-aminophenoxazine-3-one preceded by decrease of intracellular pH, depolarization of the mitocho (2011)
  • Author(s): Tabuchi T., Che X.-F.,Hiraishi K., Adachi M., Miyano K., Sumimoto H., Tabuchi T., Miyazawa K., and Tomoda A
  • Journal Title: J. Pharmacol. Sci Volume: 117 Pages: 139-48
  • URL: https://www.jstage.jst.go.jp/article/jphs/117/3/117_11134FP/_article
  • Peer Reviewed
• [Journal Article] Selectively induced apoptosis in human neutrophils in the presence of oxidative phenoxazines, 2-amino-4, 4α-dihydryo-4α-7H-phenoxazine-3-one and 2-aminophenoxazine-3-one preceded by decrease of intracellular pH, depolarization of the mitochondria and inhibition of superoxide generation. (2011)
  • Author(s): Tabuchi T., Che X.-F., Hiraishi K., Adachi M., Miyano K., Sumimoto H., Tabuchi T.
  • Journal Title: J Pharmacol Sci. Volume: 117 Pages: 139-148
  • NAID: 10030453178
  • Peer Reviewed
• [Presentation] Nox family NAPDH oxidases and redox signaling. (2012)
  • Author(s): Hideki Sumimoto, Kei Miyano
  • Organizer: 第85回日本生化学会大会:シンポジウム「Frontiers in redox signaling and oxidative stress research 」
  • Place of Presentation: 福岡
• [Presentation] アラキドン酸は、p47^<phox>の構造変化に加えてp67^<phox>-Nox2間の相互作用を誘導することにより食細胞NADPHオキシダーゼを活性化する. Arachidonic acid induces not only a conformational change of p47^<phox>but also interaction of p67^<phox>with Nox2 to activate the phagocyte NADPH oxidase. (2012)
  • Author(s): 的野 る美, 宮野 佳, 住本 英樹.
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] スーパーオキシド生成酵素NADPHオキシダーゼ5(Nox5)の細胞膜への局在化と酵素活性化に必要なN末端細胞質領域の同定.A region N-terminal to the transmembrane domain of NADPH oxidase5 (Nox5) is required for the plasma membrane localization of Nox5 and the oxidase activation. (2012)
  • Author(s): 宮野 佳, 住本 英樹
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] 活性酸素シグナル生成の制御と遺伝学 (2012)
  • Author(s): 住本 英樹,宮野 佳
  • Organizer: 日本遺伝学会第84回大会:公開シンポジウム「活性酸素シグナル伝達制御の遺伝学」
  • Place of Presentation: 福岡
• [Presentation] Nox family NAPDH oxidases and redox signaling (2012)
  • Author(s): Hideki Sumimoto et. al.
  • Organizer: 第85回日本生化学会大会: シンポジウム
  • Place of Presentation: 福岡
  • Invited
• [Presentation] アラキドン酸は、p47phoxの構造変化に加えてp67phox-Nox2間の相互作用を誘導することにより食細胞NADPHオキシダーゼを活性化する (2012)
  • Author(s): 的野 る美 et. al.
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] スーパーオキシド生成酵素NADPHオキシダーゼ5（Nox5）の細胞膜への局在化と酵素活性化に必要なN末端細胞質領域の同定 (2012)
  • Author(s): 宮野 佳 et. al.
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] 活性酸素シグナル生成の制御と遺伝学 (2012)
  • Author(s): 住本 英樹 et. al.
  • Organizer: 日本遺伝学会第84回大会: 公開シンポジウム「活性酸素シグナル伝達制御の遺伝学」
  • Place of Presentation: 福岡
  • Invited
• [Presentation] The Nox family NADPH oxidases involved in host defense and signal transduction [invited speaker] (2011)
  • Author(s): Sumimoto, H., and Miyano, K.
  • Organizer: The 13th International Congress of Bacteriology and Applied Microbiology: Symposium "ROS signaling in host-bacteria stress responses"
  • Place of Presentation: Sapporo, Japan
• [Presentation] Structure and regulation of Nox family NADPH oxidases that deliberately produce reactive oxygen species [invited speaker] (2011)
  • Author(s): Sumimoto, H., and Miyano
  • Organizer: The 17th International Symposium on Flavins and Flavoproteins.
  • Place of Presentation: Berkeley, USA
• [Presentation] 食細胞と非食細胞NADPHオキシダーゼの活性酸素生成活性の制御領域について (2011)
  • Author(s): 宮野 佳,住本 英樹
  • Organizer: 第22回日本生体防御学会学術総会
  • Place of Presentation: 那覇
• [Presentation] 活性酸素生成酵素NADPHオキシダーゼの活性調節領域について (2011)
  • Author(s): 宮野 佳, 住本 英樹
  • Organizer: 2011年度日本生化学会九州支部例会
  • Place of Presentation: 久留米
• [Presentation] 食細胞と非食細胞NADPHオキシダーゼの活性酸素生成活性の制御領域について (2011)
  • Author(s): 宮野 佳、住本 英樹
  • Organizer: 生体防御学会
  • Place of Presentation: 那覇