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Signal characteristics of heatero-receptor coupling and generation of artificial ligand

Research Project

Project/Area Number 15K14473
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionKanazawa University

Principal Investigator

Matsumoto Kunio  金沢大学, がん進展制御研究所, 教授 (90201780)

Co-Investigator(Renkei-kenkyūsha) SUGA Hiroaki  東京大学, 大学院理学系研究科, 教授 (00361668)
Research Collaborator SAKAI Katsuya  金沢大学, がん進展制御研究所, 助教 (10523318)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords細胞増殖因子 / チロシンキナーゼ / 受容体 / サイトカイン / 増殖因子受容体 / シグナル伝達 / 増殖因子 / ペプチド / HGF / MET / 特殊環状ペプチド
Outline of Final Research Achievements

Artificial ligands that induce the dimerization of growth factor receptors may be applicable to regenerative medicine, and generation of artificial ligands that have unique and novel biological activities may be possible. We here investigated signal activation by hetero-dimerization between different growth factor receptors. The split luciferase fusion protein system and observation of receptor molecules by atomic force microscopy were performed and determined to be appropriate for evaluation of growth factor receptor dimerization. Hetero-dimer formation between MET, RET, and IGF receptors was induced in cultured cells using FKBP/FRB fusion receptors, however, activation of these receptor and downstream signaling molecules were not seen. Combination of other growth factor receptors seemed to be required to further clarify possibility for generation of artificial ligands capable of inducing hetero-receptor dimerization and activation.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (23 results)

All 2017 2016 2015

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 6 results,  Acknowledgement Compliant: 5 results) Presentation (12 results) (of which Invited: 4 results) Book (2 results)

  • [Journal Article] Exome sequencing deciphers a germline MET mutation in familial epidermal growth factor receptor-mutant lung cancer.2017

    • Author(s)
      Tode N, Kikuchi T, Sakakibara T, Hirano T, Inoue A, Ohkouchi S, Tamada T, Okazaki T, Koarai A, Sugiura H, Niihori T, Aoki Y, Nakayama K, Matsumoto K, Matsubara Y, Yamamoto M, Watanabe A, Nukiwa T, Ichinose M.
    • Journal Title

      Cancer Sci

      Volume: 印刷中 Issue: 6 Pages: 1263-1270

    • DOI

      10.1111/cas.13233

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] HGF-MET in cancer progression and biomarker discovery.2017

    • Author(s)
      Matsumoto K, Umitsu M, De Silva DM, Roy A, Bottaro DP.
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 3 Pages: 296-307

    • DOI

      10.1111/cas.13156

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hepatocyte growth factor in physiology and infectious diseases.2017

    • Author(s)
      Imamura R, Matsumoto K.
    • Journal Title

      Cytokine

      Volume: in press Pages: 97-106

    • DOI

      10.1016/j.cyto.2016.12.025

    • NAID

      120006027776

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Probing conformational and functional states of human hepatocyte growth factor by a panel of monoclonal antibodies.2016

    • Author(s)
      Umitsu M, Sakai K, Ogasawara S, Kaneko M, Asaki R, Tamura-Kawakami K, Kato Y, Matsumoto K, Takagi J.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 33149-33149

    • DOI

      10.1038/srep33149

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cell-autonomous changes in Met receptor expression regulate the growth and metastatic characteristics in malignant melanoma.2016

    • Author(s)
      Adachi E, Sakai K, Nishiuchi T, Imamura R, Sato H, Matsumoto K.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 43 Pages: 70779-70793

    • DOI

      10.18632/oncotarget.12221

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Non-small cell lung cancer cells acquire resistance to the ALK inhibitor alectinib by activating alternative receptor tyrosine kinases.2016

    • Author(s)
      Isozaki H, Ichihara E, Takigawa N, Ohashi K, Ochi N, Yasugi M, Ninomiya T, Yamane H, Hotta K, Sakai K, Matsumoto K, Hosokawa S, Bessho A, Sendo T, Tanimoto M, Kiura K.
    • Journal Title

      Cancer Research

      Volume: 76 Issue: 6 Pages: 1506-1516

    • DOI

      10.1158/0008-5472.can-15-1010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Artificial human Met agonists based on macrocycle scaffolds2015

    • Author(s)
      Ito K, Sakai K, Suzuki Y, Ozawa N, Hatta T, Natsume T, Matsumoto K, Suga H.
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 6373-6373

    • DOI

      10.1038/ncomms7373

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A clinical protocol to inhibit the HGF/c-Met pathway for malignant mesothelioma with an intrapleural injection of adenoviruses expressing the NK4 gene.2015

    • Author(s)
      Tada, Y., Hiroshima, K., Shimada, H., Morishita, N., Shirakawa, T., Matsumoto, K., Shingyoji, M., Sekine, I., Tatsumi, K. and Tagawa, M.
    • Journal Title

      SpringerPlus

      Volume: 4 Issue: 1 Pages: 358-368

    • DOI

      10.1186/s40064-015-1123-3

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatocyte growth factor and Met in drug discovery2015

    • Author(s)
      Sakai H, Aoki S, Matsumoto K
    • Journal Title

      J. Biochem.

      Volume: 157 Issue: 5 Pages: 271-284

    • DOI

      10.1093/jb/mvv027

    • NAID

      120005647661

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Regulation and probing of HGF-MET by peptide-based technology.2016

    • Author(s)
      Kunio Matsumoto
    • Organizer
      The 21st Japan-Korea Cancer Research Workshop
    • Place of Presentation
      Seoul
    • Year and Date
      2016-12-23
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] HGF-MET受容体の制御・構造解析支援と創薬.2016

    • Author(s)
      松本邦夫
    • Organizer
      第4回創薬等支援技術基盤プラットフォーム公開シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2016-12-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] HGF/c-Metシグナリングの解明に向けた二本鎖HGFの構造決定.2016

    • Author(s)
      海津 正賢、有森 貴夫、酒井克也、小笠原 諭、北郷悠、金子美華、加藤幸成、松本邦夫、高木 淳一
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-12-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] Purification and functional analyses of multi-functional cytokine Lect2.2016

    • Author(s)
      今村 龍、Jangphattananont Nawaphat、酒井克也、松本邦夫
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] B16F10メラノーマの造腫瘍性/転移性におけるMet階層的発現の意義.2016

    • Author(s)
      足立恵理、酒井克也、今村龍、松本邦夫
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] EML4-ALK融合遺伝子陽性肺癌に置けるALK阻害剤耐性克服.2016

    • Author(s)
      磯崎英子、市原英基、瀧川奈義夫、松本邦夫、千堂年昭、谷本光音、木浦勝行
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 特殊環状ペプチドによる人工Metアゴニスト.2016

    • Author(s)
      Miao Wenyu、酒井克也、小澤直也、伊藤健一郎、菅裕明、松本邦夫
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター・東北大学 仙台市
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 特殊環状ペプチドによる人工細胞増殖因子の創製2016

    • Author(s)
      松本邦夫
    • Organizer
      ペプチドフォーラム
    • Place of Presentation
      金沢大学 サテライト・プラザ(石川県金沢市)
    • Year and Date
      2016-03-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 悪性黒色腫におけるMet受容体の階層的発現に連動する腫瘍特性(薬剤耐性・転移性)制御2015

    • Author(s)
      足立恵理、酒井克也、松本邦夫
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 環状ペプチドによる人工Met受容体アゴニストの創製2015

    • Author(s)
      酒井克也、伊藤健一郎、菅裕明、松本邦夫
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report
  • [Presentation] 特殊環状ペプチドによるMet/HGF受容体アゴニストの創製2015

    • Author(s)
      松本邦夫、酒井克也、伊藤健一郎、菅裕明
    • Organizer
      インターフェロン・サイトカイン学会
    • Place of Presentation
      東京工業大学(東京都目黒区大岡山)
    • Year and Date
      2015-07-18
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 特殊環状ペプチドによる人工HGFの創製2015

    • Author(s)
      松本邦夫、酒井克也、伊藤健一郎、菅裕明
    • Organizer
      肝細胞研究会
    • Place of Presentation
      米子コンベンションセンター(鳥取県米子)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
  • [Book] "HGF" サイトカイン・増殖因子キーワード事典2015

    • Author(s)
      松本邦夫
    • Total Pages
      420
    • Publisher
      羊土社
    • Related Report
      2015 Research-status Report
  • [Book] "MspとMsp受容体"サイトカイン・増殖因子キーワード事典2015

    • Author(s)
      酒井克也、松本邦夫
    • Total Pages
      420
    • Publisher
      羊土社
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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