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Involvement of small GTPase Rho family signaling pathways in diseases.

Research Project

Project/Area Number 23590357
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

AMANO Mutsuki  名古屋大学, 医学(系)研究科(研究院), 准教授 (90304170)

Co-Investigator(Kenkyū-buntansha) KAIBUCHI Kozo  名古屋大学, 大学院医学系研究科, 教授 (00169377)
Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords細胞内シグナル伝達 / リン酸化 / キナーゼ / プロテオミクス / Rho / シグナル伝達 / 細胞骨格
Outline of Final Research Achievements

In this study, we focused on the analysis of protein kinases downstream of Rho family small GTPases as therapeutic targets. We developed the novel substrate screening method based on the interactome analysis. By this method, a number of candidate substrates were identified for several kinases including Rho-kinase, PKN, and aPKC. We identified tumor suppressor protein Scrib and cardiomyopathy-related gene products such as CARP and MYL2 as novel Rho-kinase substrates. We identified phosphorylation sites, and analyzed the modes of action for Scrib and CARP upon the phosphorylation by Rho-kinase. We also found that PKA phosphorylates Rho-kinase, suggesting the crosstalk between PKA and Rho-kinase.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (15 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Invited: 1 results)

  • [Journal Article] <i>In vivo</i> Screening for Substrates of Protein Kinase A Using a Combination of Proteomic Approaches and Pharmacological Modulation of Kinase Activity2015

    • Author(s)
      Hamaguchi, T., Nakamuta, S., Funahashi, Y., Takano, T., Nishioka, T., Shohag, M.H., Yura, Y., Kaibuchi, K., and Amano, M.
    • Journal Title

      Cell Structure and Function

      Volume: 40 Issue: 1 Pages: 1-12

    • DOI

      10.1247/csf.14014

    • NAID

      130004712922

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Developing novel methods to search for substrates of protein kinases such as Rho-kinase.2015

    • Author(s)
      Nishioka, T., Shohag, M.H., Amano, M., and Kaibuchi, K.
    • Journal Title

      Biochim Biophys Acta

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preferential targeting of p39-activated Cdk5 to Rac1-induced lamellipodia.2014

    • Author(s)
      Ito, Y., Asada, A., Kobayashi, H., Takano, T., Sharma, G., Saito, T., Ohta, Y., Amano, M., Kaibuchi, K., and Hisanaga, S.
    • Journal Title

      Molecular and Cellular Neurosciences

      Volume: 61 Pages: 34-45

    • DOI

      10.1016/j.mcn.2014.05.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The inositol 5-phosphatase SHIP2 is an effector of RhoA and is involved in cell polarity and migration2012

    • Author(s)
      Kato, K.
    • Journal Title

      Mol Biol Cell

      Volume: 23 Issue: 13 Pages: 2593-604

    • DOI

      10.1091/mbc.e11-11-0958

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Distinct distribution and localization of Rho-kinase in mouse epithelial, muscle and neural tissues.2012

    • Author(s)
      Iizuka, M., Kimura, K., Wang, S., Kato, K., Amano, M., Kaibuchi, K., and Mizoguchi, A.
    • Journal Title

      Cell structure and function

      Volume: 37 Pages: 155-175

    • NAID

      130004137587

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proteomic Screening for Rho-kinase Substrates by Combining Kinase and Phosphatase Inhibitors with 14-3-3zeta Affinity Chromatography.2012

    • Author(s)
      Nishioka, T., Nakayama, M., Amano, M., and Kaibuchi, K.
    • Journal Title

      Cell structure and function

      Volume: 37 Pages: 39-48

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] リン酸化プロテオミクスによるモノアミンシグナルの解明2015

    • Author(s)
      天野睦紀
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場、愛知県、名古屋市
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Systematic Substrate Screening of Protein Kinases using a Functional Proteomic Approach2014

    • Author(s)
      Mutsuki Amano
    • Organizer
      8th International Conference Inhibitors of Protein Kinases (IPK2014)
    • Place of Presentation
      Warsaw, Poland
    • Year and Date
      2014-09-21 – 2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Protein phosphorylation remains a black box in signal transduction: Developing a new method to search for substrates of polarity kinases including Rho-kinase2014

    • Author(s)
      Mutsuki Amano
    • Organizer
      The 4th Asia Pacific Protein Association (APPA) Conference
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      2014-05-17 – 2014-05-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経関連キナーゼの基質の網羅的解析2013

    • Author(s)
      天野睦紀
    • Organizer
      第13回日本蛋白質科学学会年会
    • Place of Presentation
      とりぎん文化会館(鳥取市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 蛋白質相互作用を利用したキナーゼ基質の網羅的解析2011

    • Author(s)
      天野睦紀
    • Organizer
      日本プロテオーム学会2011年大会
    • Place of Presentation
      新潟
    • Related Report
      2011 Research-status Report
  • [Presentation] タンパク質相互作用を利用したキナーゼ基質の網羅的解析2011

    • Author(s)
      天野睦紀
    • Organizer
      第2回 神経科学と構造生物学の融合
    • Place of Presentation
      岡崎
    • Related Report
      2011 Research-status Report
  • [Presentation] 神経関連キナーゼの基質の網羅的解析

    • Author(s)
      天野睦紀
    • Organizer
      第27回日本医用マススペクトル学会東海支部講演会
    • Place of Presentation
      名古屋大学医学部附属病院(名古屋市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Systematic Substrate Screening of Protein kinases in brain by a proteomic approach

    • Author(s)
      天野睦紀
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] 神経関連キナーゼの基質の網羅的解析

    • Author(s)
      天野睦紀
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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