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精密定量プロテオミクスを用いたシグナル伝達の包括的解析

Publicly Offered Research

Project AreaIntegrative understanding of biological signaling networks based on mathematical science
Project/Area Number 17H06011
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionKyushu University

Principal Investigator

松本 雅記  九州大学, 生体防御医学研究所, 准教授 (60380531)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywordsプロテオミクス / シグナル伝達 / 定量プロテオミクス / リン酸化 / 絶対定量 / プロテオーム
Outline of Annual Research Achievements

細胞運命決定・増殖などの本質的な生命現象は細胞外刺激が引き起こす細胞内シグナル伝達によって規定されている。これまでシグナル伝達に関与するタンパク質が多数同定され、それらの間で起きる相互作用やリン酸化反応を介してシグナル伝達経路が形成されていることが示されている。一方で、同一シグナル経路が刺激の種類や強さによって異なるアウトプットを生み出す機構などはほとんど不明である。近年、シグナル伝達を数理モデルに落とし込んで理解する試みがなされているが、シグナル伝達因子の濃度情報や網羅的な飜訳後修飾のダイナミクスデータの不足が大きな障害となっている。本研究では独自に開発してきたタンパク質精密定量法iMPAQT法を応用し、細胞内シグナル伝達ネットワークにおけるタンパク質発現絶対量計測やネットワーク動態(リン酸化や相互作用の変化)計測に応用し、シグナル伝達の特異性や多様性を生み出す動作原理の解明を試みた。
現在のiMPAQT法はmTRAQ試薬を用いた質量タグの導入によって内部標準と試料ペプチドを区別しているが、より利便性や感度を高めるために、安定同位体標識アミノ酸の導入による内部標準の作製を実施した。確立された手法を用いて、数種類のがん細胞株を対象にシグナル伝達分子を対象とした絶対量計測を試みた。多くのシグナル伝達系の構成要素を検出することが可能であり、シグナル伝達経路の構造的特徴を定量化に成功した。さらに、30,000以上のリン酸化部位を同定しデータベース化し、iMPAQTのワークフローを適用し、様々な刺激に応答するリン酸化変動を計測するための計測メソッドを構築した、迅速に任意のタンパク質リン酸化を計測可能な技術を確立した。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (16 results)

All 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Tricarboxylic acid cycle activity suppresses acetylation of mitochondrial proteins during early embryonic development in Caenorhabditis elegans.2019

    • Author(s)
      Hada Kazumasa、Hirota Keiko、Inanobe Ai、Kako Koichiro、Miyata Mai、Araoi Sho、Matsumoto Masaki、Ohta Reiya、Arisawa Mitsuhiro、Daitoku Hiroaki、Hanada Toshikatsu、Fukamizu Akiyoshi
    • Journal Title

      J. Biol. Chem.

      Volume: 294 Issue: 9 Pages: 3091-3099

    • DOI

      10.1074/jbc.ra118.004726

    • NAID

      120007133475

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb162018

    • Author(s)
      Hosokawa Hiroyuki、Romero-Wolf Maile、Yui Mary A.、Ungerb?ck Jonas、Quiloan Maria L. G.、Matsumoto Masaki、Nakayama Keiichi I.、Tanaka Tomoaki、Rothenberg Ellen V.
    • Journal Title

      Nature Immunology

      Volume: 19 Issue: 12 Pages: 1427-1440

    • DOI

      10.1038/s41590-018-0238-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of the physiological substrates of PDIp, a pancreas-specific protein-disulfide isomerase family member2018

    • Author(s)
      Fujimoto Takushi、Nakamura Orie、Saito Michiko、Tsuru Akio、Matsumoto Masaki、Kohno Kenji、Inaba Kenji、Kadokura Hiroshi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 48 Pages: 18421-18433

    • DOI

      10.1074/jbc.ra118.003694

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The jPOST environment: an integrated proteomics data repository and database2018

    • Author(s)
      Moriya Yuki、Kawano Shin、Okuda Shujiro、Watanabe Yu、Matsumoto Masaki、Takami Tomoyo、Kobayashi Daiki、Yamanouchi Yoshinori、Araki Norie、Yoshizawa Akiyasu C、Tabata Tsuyoshi、Iwasaki Mio、Sugiyama Naoyuki、Tanaka Satoshi、Goto Susumu、Ishihama Yasushi
    • Journal Title

      Nucleic Acids Research

      Volume: 47 Issue: D1 Pages: 1218-1224

    • DOI

      10.1093/nar/gky899

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks2018

    • Author(s)
      Kawata Kentaro、Hatano Atsushi、Yugi Katsuyuki、Kubota Hiroyuki、Sano Takanori、Fujii Masashi、Tomizawa Yoko、Kokaji Toshiya、Tanaka Kaori Y.、Uda Shinsuke、Suzuki Yutaka、Matsumoto Masaki、Nakayama Keiichi I.、Saitoh Kaori、Kato Keiko、Ueno Ayano、Ohishi Maki、Hirayama Akiyoshi、Soga Tomoyoshi、Kuroda Shinya
    • Journal Title

      iScience

      Volume: 7 Pages: 212-229

    • DOI

      10.1016/j.isci.2018.07.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding2018

    • Author(s)
      Hosokawa Hiroyuki、Ungerb?ck Jonas、Wang Xun、Matsumoto Masaki、Nakayama Keiichi I.、Cohen Sarah M.、Tanaka Tomoaki、Rothenberg Ellen V.
    • Journal Title

      Immunity

      Volume: 48 Issue: 6 Pages: 1119-1134.e7

    • DOI

      10.1016/j.immuni.2018.04.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insulin-like growth factor 1 receptor stabilizes the ETV6-NTRK3 chimeric oncoprotein by blocking its KPC1/Rnf123-mediated proteasomal degradation2018

    • Author(s)
      Tognon, C. E., Rafn, B., Cetinbas, N. M., Kamura, T., Trigo, G., Rotblat, B., Okumura, F., Matsumoto, M., Chow, C., Davare, M., Pollak, M., Mayor, T., and Sorensen, P. H.
    • Journal Title

      J Biol Chem

      Volume: 293 Issue: 32 Pages: 12502-12515

    • DOI

      10.1074/jbc.ra117.000321

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The promise of targeted proteomics for quantitative network biology2018

    • Author(s)
      Matsumoto Masaki、Nakayama Keiichi I
    • Journal Title

      Current Opinion in Biotechnology

      Volume: 54 Pages: 88-97

    • DOI

      10.1016/j.copbio.2018.02.014

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth.2018

    • Author(s)
      M Morita, T Sato, M Nomura, Y Sakamoto, Y Inoue, R Tanaka, S Ito, K Kurosawa, K Yamaguchi, Y Sugiura, H Takizaki, Y Yamashita, R Katakura, I Sato, Y Okada, H Watanabe, G Kondoh, et al.
    • Journal Title

      Cancer Cell

      Volume: 12 Issue: 3 Pages: 355-367

    • DOI

      10.1016/j.ccell.2018.02.004

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages2017

    • Author(s)
      Nakatsumi Hirokazu、Matsumoto Masaki、Nakayama Keiichi I.
    • Journal Title

      Cell Reports

      Volume: 21 Issue: 9 Pages: 2471-2486

    • DOI

      10.1016/j.celrep.2017.11.014

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Robotic crowd biology with Maholo LabDroids.2017

    • Author(s)
      Yachie N; Robotic Biology Consortium (inc. Masaki Matsumoto)., Natsume T.
    • Journal Title

      Nature Biotechnology

      Volume: 35 Issue: 4 Pages: 310-312

    • DOI

      10.1038/nbt.3758

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] iMPAQT: a scalable and flexible platform for the quantification of proteins of interest2018

    • Author(s)
      松本 雅記、中山 敬一
    • Organizer
      第91回日本生化学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iMPAQT ver.2.0: 拡張性と柔軟性を備えたタンパク質絶対定量プラットフォーム2018

    • Author(s)
      松本 雅記、中山 敬一
    • Organizer
      MSP2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] obotics promotes accurate and reproducible data acquisition in proteomics2018

    • Author(s)
      Masaki Matsumoto
    • Organizer
      Robotics and Semantic Systems for Biology Symposium 2
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iMPAQT: A Platform for Large-Scale Targeted Proteomics Based on an in Vitro Human Proteome2017

    • Author(s)
      松本雅記、中山敬一
    • Organizer
      JPrOS2017年大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iMPAQT: A platform for large-scale targeted proteomics based on an in vitro human proteome2017

    • Author(s)
      松本雅記
    • Organizer
      第65質量分析総合討論会
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-04-28   Modified: 2019-12-27  

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