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Analysis of substrate recognition and regulatory mechanisms for protein kinases.

Research Project

Project/Area Number 17K07383
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cell biology
Research InstitutionNagoya University

Principal Investigator

Amano Mutsuki  名古屋大学, 医学系研究科, 准教授 (90304170)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsリン酸化 / プロテインキナーゼ / 細胞内シグナル伝達 / 基質 / 細胞内情報伝達 / シグナル伝達 / キナーゼ / プロテオーム
Outline of Final Research Achievements

In this study, we analyzed substrate recognition and regulatory mechanisms of protein kinases, as well as physiological and pathological functions. We identified the specific sequences of MYPT1, a substrate for Rho-kinase, as docking motifs (DMs) conferring selectivity and efficiency of phosphorylation by Rho-kinase. We also found that longer intrinsically disordered regions (IDRs) are preferably phosphorylated by stochastic simulation model using our screening dataset for 15 protein kinases. In addition, functional analyses revealed that MAPK-Npas4/MKL2 (mouse striatal neurons) and PKN-MKL1 (mouse heart) signals are involved in dopamine-induced gene expression and stress-induced cardiac dysfunction, respectively.

Academic Significance and Societal Importance of the Research Achievements

タンパク質リン酸化は細胞内シグナル伝達に中心的な役割を果たし、生理機能のみならず種々の疾患に深く関わっている。本研究では、独自に開発したキナーゼ基質スクリーニング法(KISS法)より得られたデータを基に、リン酸化シグナルを理解するための分子基盤(キナーゼの基質認識機構)、および種々のキナーゼー基質シグナルの疾患への関わりについて理解を深めることができた。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (11 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (3 results)

  • [Journal Article] Dynamic subcellular localization and transcription activity of the SRF cofactor MKL2 in the striatum are regulated by MAPK2021

    • Author(s)
      Ariza Anthony、Funahashi Yasuhiro、Kozawa Sachi、Omar Faruk Md.、Nagai Taku、Amano Mutsuki、Kaibuchi Kozo
    • Journal Title

      Journal of Neurochemistry

      Volume: - Issue: 6 Pages: 1774-1788

    • DOI

      10.1111/jnc.15303

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk2020

    • Author(s)
      Mariko Sekiguchi, Akiko Kodama,... Emiko Shishido,... Daisuke Mori, Norio Ozaki
    • Journal Title

      Translational psychiatry

      Volume: 10 Issue: 1 Pages: 1-15

    • DOI

      10.1038/s41398-020-00917-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dopamine Receptor Dop1R2 Stabilizes Appetitive Olfactory Memory through the Raf/MAPK Pathway in Drosophila2020

    • Author(s)
      Sun Huan、Nishioka Tomoki、Hiramatsu Shun、Kondo Shu、Amano Mutsuki、Kaibuchi Kozo、Ichinose Toshiharu、Tanimoto Hiromu
    • Journal Title

      The Journal of Neuroscience

      Volume: 40 Issue: 14 Pages: 2935-2942

    • DOI

      10.1523/jneurosci.1572-19.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein kinases phosphorylate long disordered regions in intrinsically disordered proteins2019

    • Author(s)
      Koike Ryotaro、Amano Mutsuki、Kaibuchi Kozo、Ota Motonori
    • Journal Title

      Protein Science

      Volume: 29 Issue: 2 Pages: 564-571

    • DOI

      10.1002/pro.3789

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein Kinase N Promotes Stress-Induced Cardiac Dysfunction Through Phosphorylation of Myocardin-Related Transcription Factor A and Disruption of Its Interaction With Actin.2019

    • Author(s)
      Sakaguchi T, Takefuji M, Wettschureck N, Hamaguchi T, Amano M, Kato K, Tsuda T, Eguchi S, Ishihama S, Mori Y, Yura Y, Yoshida T, Unno K, Okumura T, Ishii H, Shimizu Y, Bando YK, Ohashi K, Ouchi N, Enomoto A, Offermanns S, Kaibuchi K, Murohara T.
    • Journal Title

      Circulation.

      Volume: 140 Issue: 21 Pages: 1737-1752

    • DOI

      10.1161/circulationaha.119.041019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pathological Progression Induced by the Frontotemporal Dementia-Associated R406W Tau Mutation in Patient-Derived iPSCs2019

    • Author(s)
      Nakamura Mari、Shiozawa Seiji、Tsuboi Daisuke、Amano Mutsuki、Watanabe Hirotaka、Maeda Sumihiro、Kimura Taeko、Yoshimatsu Sho、Kisa Fumihiko、Karch Celeste M.、Miyasaka Tomohiro、Takashima Akihiko、Sahara Naruhiko、Hisanaga Shin-ichi、Ikeuchi Takeshi、Kaibuchi Kozo、Okano Hideyuki
    • Journal Title

      Stem Cell Reports

      Volume: 13 Issue: 4 Pages: 684-699

    • DOI

      10.1016/j.stemcr.2019.08.011

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphorylation of Npas4 by MAPK Regulates Reward-Related Gene Expression and Behaviors2019

    • Author(s)
      Funahashi Yasuhiro、Ariza Anthony、Emi Ryosuke、Xu Yifan、Shan Wei、Suzuki Ko、Kozawa Sachi、Ahammad Rijwan Uddin、Wu Mengya、Takano Tetsuya、Yura Yoshimitsu、Kuroda Keisuke、Nagai Taku、Amano Mutsuki、Yamada Kiyofumi、Kaibuchi Kozo
    • Journal Title

      Cell Reports

      Volume: 29 Issue: 10 Pages: 3235-3252.e9

    • DOI

      10.1016/j.celrep.2019.10.116

    • NAID

      130007812598

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive analysis of kinase-oriented phospho-signalling pathways2018

    • Author(s)
      Amano Mutsuki、Nishioka Tomoki、Tsuboi Daisuke、Kuroda Keisuke、Funahashi Yasuhiro、Yamahashi Yukie、Kaibuchi Kozo
    • Journal Title

      The Journal of Biochemistry

      Volume: 165 Issue: 4 Pages: 301-307

    • DOI

      10.1093/jb/mvy115

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Balance between dopamine and adenosine signals regulates the PKA/Rap1 pathway in striatal medium spiny neurons2018

    • Author(s)
      Zhang XJ, Nagai T, Ahammad RU, Kuroda K, Nakamuta S, Nakano T, Yukinawa N, Funahashi Y, Yamahashi Y, Amano M, Yoshimoto J, Yamada K, and Kaibuchi K.
    • Journal Title

      Neurochemistry International

      Volume: 122 Pages: 8-18

    • DOI

      10.1016/j.neuint.2018.10.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Targeting Tyro3 ameliorates a model of PGRN-mutant FTLD-TDP via tau-mediated synaptic pathology2018

    • Author(s)
      Fujita Kyota、Chen Xigui、Homma Hidenori、Tagawa Kazuhiko、Amano Mutsuki、Saito Ayumu、Imoto Seiya、Akatsu Hiroyasu、Hashizume Yoshio、Kaibuchi Kozo、Miyano Satoru、Okazawa Hitoshi
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 433-433

    • DOI

      10.1038/s41467-018-02821-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Discovery of long-range inhibitory signaling to ensure single axon formation2017

    • Author(s)
      Takano Tetsuya、Wu Mengya、Nakamuta Shinichi、Naoki Honda、Ishizawa Naruki、Namba Takashi、Watanabe Takashi、Xu Chundi、Hamaguchi Tomonari、Yura Yoshimitsu、Amano Mutsuki、Hahn Klaus M.、Kaibuchi Kozo
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 33-33

    • DOI

      10.1038/s41467-017-00044-2

    • NAID

      120006325188

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] インタラクトームを基盤としたタンパク質キナーゼの基質探索2019

    • Author(s)
      天野睦紀、貝淵弘三
    • Organizer
      日本プロテオーム学会2019年大会・第70回日本電気泳動学会総会 合同大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] KANPHOS Platform: A comprehensive database for kinase-associated neural phosphorylation signaling2019

    • Author(s)
      天野睦紀、西岡朋生、吉本潤一郎、観音隆幸、臼井支朗、貝淵弘三
    • Organizer
      第71回日本細胞生物学会大会・第19回日本タンパク質科学学会年会 合同年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] KANPHOS Platform:S comprehesive database for kinase-associated eural phosphorylation signaling2018

    • Author(s)
      天野睦紀
    • Organizer
      第70回日本細胞生物学会 第51回日本発生生物学会合同大会
    • Related Report
      2018 Research-status Report
  • [Presentation] KANPHOS Platform: A comprehensive database for kinase-associated neural phosphorylation signaling2018

    • Author(s)
      Mutsuki Amano
    • Organizer
      WCP2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] KANPHOS (Kinase-Associated Phospho-Signaling) Platform ―新規リン酸化DBプラットフォーム―2017

    • Author(s)
      天野睦紀、西岡朋生、黒田啓介、吉本潤一郎、観音隆幸、臼井支朗、貝淵弘三
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] リン酸化プロテオミクスによるニューロモジュレーターシグナルの解明2017

    • Author(s)
      天野睦紀
    • Organizer
      第39回神経組織培養研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Remarks] KANPHOS

    • URL

      https://kanphos.neuroinf.jp/

    • Related Report
      2020 Annual Research Report
  • [Remarks] KANPHOS (Kinase-Associated Phospho-Signaling)

    • URL

      https://kanphos.neuroinf.jp

    • Related Report
      2019 Research-status Report 2018 Research-status Report
  • [Remarks] 神経リン酸化シグナルデータベース(KANPHOS)

    • URL

      https://kanphos.neuroinf.jp/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

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