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Phosphorylation netowork analysis based on in vitro kinase-substrate relationships

Research Project

Project/Area Number 16K07198
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Genome biology
Research InstitutionKyoto University

Principal Investigator

Naoyuko Sugiyama  京都大学, 薬学研究科, 准教授 (50545704)

Research Collaborator NIINAE Tomoya  
YOSHIKAWA Yuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsプロテオミクス / シグナル伝達 / タンパク質キナーゼ / プロテオーム / 分析化学 / 細胞・組織
Outline of Final Research Achievements

To analyze a comprehensive overview of intracellular phosphorylation networks, we constructed phosphorylation model of individual human protein kinase based on in vitro kinase-substrate relationships, and developed a method for prediction of physiological kinase substrates.
The predicted kinase-substrate relationships were evaluated by using a large-scale quantitative phosphoproteome profiling, in which cultured cells were treated with or without a kinase inhibitor. Responsible kinases for the downregulated phosphorylation sites were predicted using the our method. As a result, we successfully predicted inhibition of targeted and its downstream kinases and found that the prediction accuracy is higher than that of the existing techniques.

Academic Significance and Societal Importance of the Research Achievements

タンパク質のリン酸化は細胞内のシグナル伝達に非常に重要な役割を果たしており、リン酸化酵素であるキナーゼの異常は様々な疾患と関連があることが知られている。本研究では、細胞内情報伝達ネットワークの全体像の解明を目的として、細胞内に存在するキナーゼ群の基質となるタンパク質を予測する方法を開発した。
本研究によって開発した方法を用いて各キナーゼの詳細な機能や細胞内リン酸化ネットワークの全体像が明らかとなれば、タンパク質のリン酸化異常が関与する多くの疾病のメカニズム解明や病気の診断や層別化、新規な分子標的薬の開発につながることが期待できる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results) Remarks (2 results)

  • [Journal Article] Selected Reaction Monitoring of Kinase Activity-Targeted Phosphopeptides2019

    • Author(s)
      Chisato TAKAHASHI, Tatsuya YAZAKI, Naoyuki SUGIYAMA, Yasushi ISHIHAMA
    • Journal Title

      CHROMATOGRAPHY

      Volume: 40 Issue: 2 Pages: 39-47

    • DOI

      10.15583/jpchrom.2019.005

    • NAID

      130007676149

    • ISSN
      1342-8284, 1348-3315
    • Year and Date
      2019-06-20
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative proteomics of Helicobacter pylori strains reveals geographical features rather than genomic variations2019

    • Author(s)
      Sugiyama Naoyuki、Miyake Satomi、Lin Miao‐Hsia、Wakabayashi Masaki、Marusawa Hiroyuki、Nishiumi Shin、Yoshida Masaru、Ishihama Yasushi
    • Journal Title

      Genes to Cells

      Volume: 24 Issue: 2 Pages: 139-150

    • DOI

      10.1111/gtc.12662

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Phosphoproteomic profiling reveals ABA-responsive phosphosignaling pathways in Physcomitrella patens2018

    • Author(s)
      Amagai Anna、Honda Yoshimasa、Ishikawa Shinnosuke、Hara Yurie、Kuwamura Mayuri、Shinozawa Akihisa、Sugiyama Naoyuki、Ishihama Yasushi、Takezawa Daisuke、Sakata Yoichi、Shinozaki Kazuo、Umezawa Taishi
    • Journal Title

      The Plant Journal

      Volume: 94 Issue: 4 Pages: 699-708

    • DOI

      10.1111/tpj.13891

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blue light and CO2 signals converge to regulate light-induced stomatal opening2017

    • Author(s)
      Hiyama Asami、Takemiya Atsushi、Munemasa Shintaro、Okuma Eiji、Sugiyama Naoyuki、Tada Yasuomi、Murata Yoshiyuki、Shimazaki Ken-ichiro
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1284-1284

    • DOI

      10.1038/s41467-017-01237-5

    • NAID

      120006368181

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identifications of Putative PKA Substrates with Quantitative Phosphoproteomics and Primary-Sequence-Based Scoring.2017

    • Author(s)
      Imamura H, Wagih O, Niinae T, Sugiyama N, Beltrao P, Ishihama Y
    • Journal Title

      J Proteome Res

      Volume: 16 Issue: 4 Pages: 1825-1830

    • DOI

      10.1021/acs.jproteome.7b00087

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] jPOSTrepo: an international standard data repository for proteomes.2017

    • Author(s)
      Okuda S, Watanabe Y, Moriya Y, Kawano S, Yamamoto T, Matsumoto M, Takami T, Kobayashi D, Araki N, Yoshizawa AC, Tabata T, Sugiyama N, Goto S, Ishihama Y.
    • Journal Title

      Nucleic Acids Res.

      Volume: 45 Issue: D1 Pages: D1107-D1111

    • DOI

      10.1093/nar/gkw1080

    • NAID

      120006353864

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 細菌叢の高深度メタプロテオーム解析2019

    • Author(s)
      杉山直幸
    • Organizer
      Meta-Omics Workshop in Kyoto 2019
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] キナーゼ収斂リン酸化プロテオミクスを用いた分子標的薬プロファイリング2019

    • Author(s)
      吉川侑樹・杉山直幸・石濱泰
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] キノームプロファイリングによるリン酸化ネットワーク解析2018

    • Author(s)
      杉山直幸・ 今村春菜・ 坂本大・ 中園純菜・ 八児一隆・ 高橋知里・ Hsin-yi, Chang・ 石濱泰
    • Organizer
      日本質量分析学会・日本プロテオーム学会 2018年合同大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Direct Profiling of Kinome Activities Using Kinase-Specific Substrate Peptides2018

    • Author(s)
      Naoyuki Sugiyama, Dai Sakamoto, Junna Nakazono, Kazutaka Yachigo, Hsin-Yi Chang, Yasushi Ishihama
    • Organizer
      25th International Symposium on Electro- and Liquid Phase-Separation Techniques(ITP2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phosphoproteome and Kinome Profiling Using NanoLC-MS/MS2018

    • Author(s)
      Naoyuki Sugiyama
    • Organizer
      2nd International BMS Symposium 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Human Kinome Profiling using Phosphoproteomic Approaches2018

    • Author(s)
      Naoyuki Sugiyama , Yasushi Ishihama
    • Organizer
      KBMSS2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] リン酸化プロテオーム解析技術を用いたキノームプロファイリング2017

    • Author(s)
      杉山直幸、石濱 泰
    • Organizer
      第77回分析化学討論会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] プロテオミクスを用いたキナーゼ収斂型シグナルネットワーク解析2017

    • Author(s)
      杉山直幸、石濱 泰
    • Organizer
      質量分析フォーラム2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Profiling Kinome Activities Using Kinase-Specific Substrate Peptides2016

    • Author(s)
      3.Naoyuki Sugiyama, Dai Sakamoto, Haruna Imamura, Pasrawin Taechawattananant, Natsumi Ishikawa, Masaki Wakabayashi, Yasushi Ishihama
    • Organizer
      HUPO2016
    • Place of Presentation
      台北(台湾)
    • Year and Date
      2016-09-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] データベース構築とキナーゼ基質予測を用いた大規模発現/翻訳語修飾プロテオーム解析2016

    • Author(s)
      2.杉山直幸、三宅里美、坂本 大、Pasrawin Taechawattananant、若林真樹、石濱 泰
    • Organizer
      ヒトプロテオーム学会2016年大会
    • Place of Presentation
      北里大学薬学部(東京)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒトキノームの基質特異性および活性プロファイリング2016

    • Author(s)
      1.杉山直幸、坂本 大、今村春菜、Pasrawin Taechawattananant、 石川奈津美、若林真樹、石濱 泰
    • Organizer
      第29回バイオメディカル分析科学シンポジウム
    • Place of Presentation
      京都大学桂キャンパス(京都)
    • Year and Date
      2016-07-28
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都大学薬学研究科 石濱研究室

    • URL

      http://www.pharm.kyoto-u.ac.jp/seizai/

    • Related Report
      2018 Annual Research Report 2016 Research-status Report
  • [Remarks] 製剤機能解析学分野 ホーム - 京都大学大学院薬学研究科・京都大学薬学部

    • URL

      http://www.pharm.kyoto-u.ac.jp/seizai/

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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