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Regulation of Raf-1 kinase through PP1 signaling

Research Project

Project/Area Number 19K06573
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 43030:Functional biochemistry-related
Research InstitutionOkayama University of Science

Principal Investigator

Eto Masumi  岡山理科大学, 獣医学部, 教授 (20232960)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsCell signaling / ホスファターゼシグナル / プロテオステーシス / BioID / mTurbo / RNAマイクロアレイ / 酵母ツーハイブリッド / BioID法 / KAT-WB / キナーゼ活性検出法 / プロテインホスファターゼ / Raf-1 / 細胞シグナリング
Outline of Research at the Start

本研究の目的は、申請者が発見した新しい細胞内シグナル伝達タンパク質の生理的な機能を解明し、得られた知見に基づき細胞機能を正常化できるかを検証することである。これまでに行った予備実験結果から細胞の生死を調節しているRaf-1キナーゼが関与していることが明らかになっている。本研究では、培養細胞を用いて細胞の生死を指標にしながら細胞内のRaf-1活性を測定するとともに、Raf-1活性に異常を持つ細胞系を用いてこの経路を正常化する方法を探る。

Outline of Final Research Achievements

The goal of this study was to understand the function of PHI-1, a regulatory protein of PP1, the major Ser/Thr phosphatase, and its role in the cell. PHI-1 has been suggested to play important roles in cellular processes and signal transduction, although the function was largely unknown. In this study, we performed experiments including expression analysis of PHI-1, gene knockdown, association with the EGF signaling pathway, and analysis of Raf-1 regulation by PHI-1, providing new insights into the function of PHI-1 and its intracellular role. In addition, we developed a new unknown kinase detection method.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、PP1調節タンパク質であるPHI-1の機能解明に貢献しました。PHI-1の細胞内での役割が明らかになることで、PP1を介した細胞のシグナル伝達や病理学的な変化に関与するメカニズムを理解する上で重要な情報となります。さらに、PHI-1が関与する細胞増殖やアポトーシス制御などの生理的プロセスの理解は、がんや他の疾患の発症や進行に関連することが示唆されました。したがって、本研究の成果は、細胞生物学や病態生理学の研究分野において新たな知識を提供し、将来的には新しい治療法や治療標的の開発につながる可能性があります。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (19 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results)

  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] トマスジェファソン大学(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Thomas Jefferson University(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Thomas Jefferson University(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Possible roles of N- and C-terminal unstructured tails of CPI-17 in regulating Ca<sup>2+</sup> sensitization force of smooth muscle2022

    • Author(s)
      Eto M, Katsuki S, Ohashi M, Miyagawa Y, Tanaka Y, Takeya K, Kitazawa T.
    • Journal Title

      Journal of Smooth Muscle Research

      Volume: 58 Issue: 0 Pages: 22-33

    • DOI

      10.1540/jsmr.58.22

    • ISSN
      0916-8737, 1884-8796
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Overexpression of progranulin increases pathological protein accumulation by suppressing autophagic flux2022

    • Author(s)
      Tanaka Yoshinori、Kusumoto Shun-ya、Honma Yuki、Takeya Kosuke、Eto Masumi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 611 Pages: 78-84

    • DOI

      10.1016/j.bbrc.2022.04.064

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MARK2 regulates directed cell migration through modulation of myosin II contractility and focal adhesion organization2022

    • Author(s)
      Pasapera Ana M.、Heissler Sarah M.、Eto Masumi、Nishimura Yukako、Fischer Robert S.、Thiam Hawa R.、Waterman Clare M.
    • Journal Title

      Current Biology

      Volume: 32 Issue: 12 Pages: 2704-2718.e6

    • DOI

      10.1016/j.cub.2022.04.088

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abemaciclib and Vacuolin-1 induce vacuole-like autolysosome formation A new tool to study autophagosome-lysosome fusion2022

    • Author(s)
      Tanaka Yoshinori、Hino Hirotsugu、Takeya Kosuke、Eto Masumi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 614 Pages: 191-197

    • DOI

      10.1016/j.bbrc.2022.05.027

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A temporal Ca<sup>2+</sup> desensitization of myosin light chain kinase in phasic smooth muscles induced by CaMKKβ/PP2A pathways2021

    • Author(s)
      Kitazawa Toshio、Matsui Toshiyasu、Katsuki Shuichi、Goto Akira、Akagi Kai、Hatano Naoya、Tokumitsu Hiroshi、Takeya Kosuke、Eto Masumi
    • Journal Title

      American Journal of Physiology-Cell Physiology

      Volume: 321 Issue: 3 Pages: C549-C558

    • DOI

      10.1152/ajpcell.00136.2021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Kinase activity-tagged western blotting assay2020

    • Author(s)
      Eto Masumi、Katsuki Shuichi、Tanaka Yoshinori、Takeya Kosuke
    • Journal Title

      BioTechniques

      Volume: 68 Issue: 4 Pages: 211-213

    • DOI

      10.2144/btn-2019-0136

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Dysmotility of gastrointestinal smooth muscles through Ca2+ sensitization/desensitization pathways2022

    • Author(s)
      江藤真澄
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Raf-1プロテオステーシスを調節する新規PP1シグナル2022

    • Author(s)
      Masumi Eto, Jason Kirkbride, Garbo Young
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dysmotility of gastrointestinal smooth muscle through Ca2+-sensitization/desensitization pathways2022

    • Author(s)
      江藤真澄
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] CaMKKb経路を介した平滑筋MLCKの 一時的なカルシウム脱感作2021

    • Author(s)
      江藤真澄、北澤俊雄、松井利康、勝木秀一、赤木魁、 後藤旭、波多野直哉、竹谷浩介、徳光浩
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Rubratoxin A-sensitive pathways responsible for temporal regulation for balancing kinase/phosphatase activities2020

    • Author(s)
      Masumi Eto, Toshiyasu Matsui, Kosuke Takeya, Kai Akagi, Shuichi Katsuki, Naoya Hatano, Hiroshi Tokumitsu and Toshio Kitazawa
    • Organizer
      14th International Conference on Protein Phosphatase
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 平滑筋Ca2+ sensitization forceの調節機構―CPI-17 N・C末端領域の生理的役割2020

    • Author(s)
      勝木秀一、大橋南海、竹谷浩介、田中良法、北澤俊雄、江藤真澄
    • Organizer
      第62回日本平滑筋学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] New Pathways That Regulate Myosin Light Chain Kinase And Cellular Force Development2019

    • Author(s)
      Masumi Eto, Toshiyasu Matsui, Kosuke Takeya, Akagi, Shuichi Katsuki, Naoya Hatano, Hiroshi Tokumitsu and Toshio Kitazawa
    • Organizer
      2019 ASCB-EMBO Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 平滑筋の興奮収縮連関を調節する新規キナーセカスケートシクナル2019

    • Author(s)
      江藤 真澄、北澤 俊雄、松井 利康、赤木 魁、 波多野 直哉、 勝木 秀一、竹谷 浩介、徳光 浩
    • Organizer
      第61回日本平滑筋学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 平滑筋の興奮収縮連関を調節する新しい薬理学的標的シグナル2019

    • Author(s)
      江藤 真澄
    • Organizer
      第140回日本薬理学会関東部会
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-04-18   Modified: 2024-01-30  

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