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2013 Fiscal Year Final Research Report

A search for novel histidine-based protein phosphatases and structural analysis of their substrate specificities

Research Project

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Project/Area Number 24659027
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionNagasaki University

Principal Investigator

TAKEDA Kohsuke  長崎大学, 医歯(薬)学総合研究科, 教授 (10313230)

Project Period (FY) 2012-04-01 – 2014-03-31
Keywordsシグナル伝達 / ストレス応答 / プロテインホスファターゼ
Research Abstract

We have recently identified PGAM5 as a novel type of protein phosphatase that relies on a histidine residue as a catalytic center; however, its mechanism of enzymatic action has not been revealed. In the current study, we found by structural analyses that the catalytic center of PGAM5 consists of two histidines and two arginines. We also found that PGAM5 forms a dimer and that the dimerization is required for the catalytic activity of PGAM5. These results provide important clues to the mechanism of action of the histidine-based protein phosphatases.

  • Research Products

    (33 results)

All 2014 2013 2012 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (19 results) Book (2 results) Remarks (1 results)

  • [Journal Article] The expression of Fn14 via mechanical stress-activated JNK contributes to apoptosis induction in osteoblasts2014

    • Author(s)
      Matsui, H., Fukuno, N., Kanda, Y., Kantoh, Y., Chida, T., Nagaura, Y., Suzuki, O., Nishitoh, H., Takeda, K., Ichijo, H., Sawada, Y., Sasaki, K., Kobayashi, T. and Tamura, S.
    • Journal Title

      J. Biol. Chem.

      Volume: 289 Pages: 6138-6450

    • Peer Reviewed
  • [Journal Article] SOD1 as a molecular switch for initiating the homeostatic ER stress response under zinc deficiency2013

    • Author(s)
      Homma, K., Fujisawa, T., Tsuburaya, N., Yamaguchi, N., Kadowaki, H., Takeda, K., Nishitoh, H., Matsuzawa, A., Naguro, I. and Ichijo, H.
    • Journal Title

      Mol. Cell

      Volume: 52 Pages: 75-86

    • Peer Reviewed
  • [Journal Article] Involvement of ASK1-p38 pathway in the pathogenesis of diabetes triggered by pancreaticβcell exhaustion2013

    • Author(s)
      Yamaguchi, K., Takeda, K., Kadowaki, H., Ueda, I., Namba, Y., Ouchi, Y., Nishitoh, H. and Ichijo, H.
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1830 Pages: 3656-3663

    • Peer Reviewed
  • [Journal Article] Atypical protein phosphatases : emerging players in cellular signaling2013

    • Author(s)
      Sadatomi, D., Tanimura, S., Ozaki, K. and Takeda, K.
    • Journal Title

      Int. J . Mol. Sci.

      Volume: 14 Pages: 4596-4612

    • Peer Reviewed
  • [Journal Article] Therapeutic targets in the ASK1-dependent stress signalling pathways2012

    • Author(s)
      Hayakawa, R., Hayakawa, T., Takeda, K. and Ichijo, H.
    • Journal Title

      Proc. J pn. Acad. Ser. B Phys. Biol. Sci.

      Volume: 88 Pages: 434-453

    • Peer Reviewed
  • [Journal Article] The phosphorylation-dependent regulation of mitochondrial proteins in stress responses2012

    • Author(s)
      Kanamaru, Y., Sekine, S., Ichijo, H. and Takeda, K.
    • Journal Title

      J. Signal Transduct.

      Volume: 2012 Pages: 931215

    • Peer Reviewed
  • [Journal Article] ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney2012

    • Author(s)
      Naguro, I., Umeda, T., Kobayashi, Y., Maruyama, J.
    • Journal Title

      Nat. Commun.

      Volume: 3 Pages: 1285

    • Peer Reviewed
  • [Journal Article] The kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP52012

    • Author(s)
      Sekine, Y., Hatanaka, R., Watanabe, T., Sono, N., Iemura, S., Natsume, T., Kuranaga, E., Miura, M., Takeda, K. and Ichijo, H.
    • Journal Title

      Mol. Cell

      Volume: 48 Pages: 692-704

    • Peer Reviewed
  • [Journal Article] Apoptosis signal-regulating kinase -1 inhibitor as a potent therapeutic drug for the treatment of gastric cancer2012

    • Author(s)
      Hayakawa, Y., Hirata, Y., Sakitani, K., Nakagawa, H., Nakata, W., Kinoshita, H., Takahashi, R., Takeda, K., Ichijo, H., Maeda, S. and Koike, K.
    • Journal Title

      Cancer Sci

      Volume: 103 Pages: 2181-2185

    • Peer Reviewed
  • [Journal Article] Rhomboid protease PARL mediates the mitochondrial membrane potential loss-induced cleavage of PGAM52012

    • Author(s)
      Sekine, S., Kanamaru, Y., Koike, M., Nishihara, A., Okada, M., Kinoshita, H., Kamiyama, M., Maruyama, J., Uchiyama, Y., Ishihara, N., Takeda, K. and Ichijo, H.
    • Journal Title

      J. Biol. Chem.

      Volume: 287 Pages: 34635-34645

    • Peer Reviewed
  • [Journal Article] A novel monoclonal antibody reveals a conformational alteration shared by amyotrophic lateral sclerosis-linked SOD1 mutants2012

    • Author(s)
      Fujisawa, T., Homma, K., Yamaguchi, N., Kadowaki, H., Tsuburaya, N., Naguro, I., Matsuzawa, A., Takeda, K., Takahashi, Y., Goto, J., Tsuji, S., Nishitoh, H. and Ichijo, H.
    • Journal Title

      Ann. Neurol.

      Volume: 72 Pages: 739-749

    • Peer Reviewed
  • [Presentation] Roles of mitochondrial sensing and responding to stress in inflammation regulation2014

    • Author(s)
      Takeda, K
    • Organizer
      The 1st International Symposium Dejima Challenge for Therapeutic Innovation
    • Place of Presentation
      長崎
    • Year and Date
      2014-03-14
  • [Presentation] ミトコンドリア局在プロテインホスファターゼPGAM5によるストレス応答制御2014

    • Author(s)
      武田弘資
    • Organizer
      第6回日本プロテインホスファターゼ研究会学術集会
    • Place of Presentation
      三重
    • Year and Date
      2014-02-21
  • [Presentation] Microvesicles形成メカニズムの解明2013

    • Author(s)
      門田善法、竹之内彰吾、尾崎惠一、武田弘資、谷村進
    • Organizer
      第30回日本薬学会九州支部大会
    • Place of Presentation
      長崎
    • Year and Date
      2013-12-08
  • [Presentation] ヒストン脱アセチル化酵素阻害剤に対する感受性におけるp21の役割2013

    • Author(s)
      田渕祐輔、小野真依、柿本貴子、谷村進、武田弘資、尾崎惠一
    • Organizer
      第30回日本薬学会九州支部大会
    • Place of Presentation
      長崎
    • Year and Date
      2013-12-07
  • [Presentation] ミトコンドリア局在型フォスファターゼPGAM5は、インスリン受容体基質のセリン/スレオニンリン酸化と安定性の調節に機能しているミトコンドリア局在型フォスファターゼPGAM5は、インスリン受容体基質のセリン/スレオニンリン酸化と安定性の調節に機能している2013

    • Author(s)
      米山鷹介、鋳延淳一、木田友佳子、福嶋俊明、関根史織、浅野知一郎、千田和広、武田弘資、高橋伸一郎
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      佐賀
    • Year and Date
      2013-12-05
  • [Presentation] ミトコンドリアのストレス受容・応答機構と炎症制御2013

    • Author(s)
      武田弘資
    • Organizer
      さきがけ研究報告会「炎症の慢性化機構の解明と制御」
    • Place of Presentation
      東京
    • Year and Date
      2013-11-10
  • [Presentation] ミトコンドリアのストレス感知機構と細胞応答2013

    • Author(s)
      武田弘資
    • Organizer
      宮崎大学大学院特別セミナー
    • Place of Presentation
      宮崎
    • Year and Date
      2013-09-20
  • [Presentation] ASK1は接触過敏における惹起相でのIL-17産生に重要である2013

    • Author(s)
      水上潤哉、武田弘資、一條秀憲、坪井良治
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-13
  • [Presentation] ゲノムワイドsiRNAスクリーニングによるミトコンドリア局在型ホスファターゼPGAM5の切断制御因子の網羅的探索2013

    • Author(s)
      金丸雄祐、関根史織、武田弘資、一條秀憲
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-12
  • [Presentation] ミトコンドリア局在型プロテインホスファターゼPGAM5の膜内切断2013

    • Author(s)
      関根史織、武田弘資、一條秀憲
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-12
  • [Presentation] Myosin1EはCaveolin1-Cavin1/3複合体の安定化を介して細胞運動を促進する2013

    • Author(s)
      谷村進、浜松絢子、木原康孝、大山要、武田弘資、河野通明
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2013-09-11
  • [Presentation] Myosin1E-SH3P2複合体による細胞運動制御の分子機構2013

    • Author(s)
      谷村進、木原康孝、大山要、中原康子、平田弦也、松丸由美、武田弘資、河野通明
    • Organizer
      平成25年度日本生化学会九州支部例会
    • Place of Presentation
      佐賀
    • Year and Date
      2013-05-18
  • [Presentation] ミトコンドリア機能低下の感知システムとしてのプロテインホスファターゼPGAM5の膜内切断2013

    • Author(s)
      武田弘資
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Year and Date
      2013-03-28
  • [Presentation] ミトコンドリアのストレス受容・応答機構と炎症制御2013

    • Author(s)
      武田弘資
    • Organizer
      創薬シンポジウム : アカデミア創薬と探索医療
    • Place of Presentation
      長崎
    • Year and Date
      2013-03-19
  • [Presentation] Role of mitochondrial protein phosphatase PGAM5 in inflammation2013

    • Author(s)
      Sadatomi, D. Takeda, K.
    • Organizer
      10th International Conference on Protein Phosphatase
    • Place of Presentation
      東京
    • Year and Date
      2013-02-28
  • [Presentation] Role of mitochondrial phosphatase PGAM5 in inflammation2013

    • Author(s)
      Takeda, K
    • Organizer
      JST-CREST International Symposium, Frontiers in Immunology and Inflammation : From Molecules to Disease
    • Place of Presentation
      東京
    • Year and Date
      2013-02-12
  • [Presentation] Regulation of cellular stress response by mitochondrial protein phosphatase PGAM52013

    • Author(s)
      Takeda, K
    • Organizer
      1st International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
    • Place of Presentation
      東京
    • Year and Date
      2013-02-01
  • [Presentation] ミトコンドリア局在プロテインホスファターゼPGAM5によるストレス応答制御2012

    • Author(s)
      武田弘資
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2012-12-07
  • [Presentation] Role of mitochondrial phosphatase PGAM5 in inflammation2012

    • Author(s)
      Takeda, K
    • Organizer
      The 12th Biennial International Endotoxicin & Innate Immunity Society Meeting (IEIIS2012)
    • Place of Presentation
      東京
    • Year and Date
      2012-10-24
  • [Book] Roles for the stress-responsive kinases ASK1 and ASK2 in tumorigenesis. Chembiomolecular Science : At the Frontier of Chemistry and Biology.2012

    • Author(s)
      Kamiyama, M., Sato, T., Takeda, K. and Ichijo, H.(eds Shibasaki, M., Iino, M. and Osada, H)
    • Total Pages
      145-154
    • Publisher
      Springer Japan
  • [Book] がんと炎症, 「がん増殖と悪性化の分子機構」2012

    • Author(s)
      武田弘資
    • Total Pages
      191-205
    • Publisher
      化学同人
  • [Remarks]

    • URL

      http://www.ph.nagasaki-u.ac.jp/lab/cell/index-j.html

URL: 

Published: 2015-06-25  

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