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Semi-synthesis of receptor tyrosine kinase and its structure and function analysis

Research Project

Project/Area Number 24687013
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Structural biochemistry
Research InstitutionOsaka University

Principal Investigator

Sato Takeshi  大阪大学, たんぱく質研究所, 講師 (90403013)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥27,170,000 (Direct Cost: ¥20,900,000、Indirect Cost: ¥6,270,000)
Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2013: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords膜タンパク質 / 半合成 / 膜貫通―膜近傍部位 / 構造生物学 / 受容体型チロシンキナーゼ / 固体NMR / 膜貫通部位 / 膜近傍部位 / 線維芽細胞増殖因子受容体 / ライゲーション
Outline of Final Research Achievements

Receptor tyrsine kinase is a transmembrane receptor which initiates a signaling for cell growth and differentiation. Dysfunction of the receptor can be a cause of cancer. In thie project, focuing on the transmembrane-juxtamembrane region of the receptor, which has been one of the most difficult portions in the field of structural biology, the structural analysis was performed. Results provided a new concept in the activation mechanism of receptor tyrosine kinase, which is the release of the intracellular juxtamembrane region form the inner leaflet of the plasma membrane. Also, the strategy of its semi-synthesis is developed. Semi-synthesis chemistry to couple expressed protein and chemically synthesized protein fragments. A portion of the receptor, from the extracellular region to the transmembrane-itracellular juxtamembrane region, was successfully synthesized.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (30 results)

All 2016 2015 2014 2013 2012 Other

All Int'l Joint Research (2 results) Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Acknowledgement Compliant: 1 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 7 results)

  • [Int'l Joint Research] Stony Brook University(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Université catholique de Louvain(ベルギー)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Synthetic transmembrane-juxtamembrane peptide for the structure and function of ErbB receptor tyrosine kinase2016

    • Author(s)
      Takeshi Sato
    • Journal Title

      Biopolymers Peptide Science

      Volume: 未定 Issue: 4 Pages: 613-621

    • DOI

      10.1002/bip.22775

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] His499 Regulates Dimerization and Prevents Oncogenic Activation by Asparagine Mutations of the Human Thrombopoietin Receptor2015

    • Author(s)
      Emilie Leroy, Jean-Philippe Defour, Takeshi Sato, Sharmila Dass, Vitalina Gryshkova, Shwe Myat Marlar, Judith Staerk, Stefan N. Constantinescu and Steven O. Smith
    • Journal Title

      J.Biol.Chem

      Volume: 291 Issue: 6 Pages: 2974-2987

    • DOI

      10.1074/jbc.m115.696534

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cooperative roles of hydrophilic loop 1 and the C terminus of presenilin 1 in the substrate-gating mechanism of γ-secretase.2015

    • Author(s)
      Shizuka Takagi-Niidome, Tomoki Sasaki, Satoko Osawa, Takeshi Sato, Kanan Morishima, Tetsuo Cai, Takeshi Iwatsubo, and Taisuke Tomita
    • Journal Title

      J. Neurosci.

      Volume: 35 Issue: 6 Pages: 2646-2656

    • DOI

      10.1523/jneurosci.3164-14.2015

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Cyclic KLVFF-Derived Peptide Aggregation Inhibitor Induces the Formation of Less Toxic Off-Pathway Amyloid Oligomers2014

    • Author(s)
      Tadamasa Arai, Daisuke Sasaki, Takushi Araya, Takeshi Sato, Youhei Sohma and Motomu Kanai
    • Journal Title

      ChemBioChem

      Volume: 17 Issue: 17 Pages: 2577-2583

    • DOI

      10.1002/cbic.201402430

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coupling of transmembrane helix orientation to membrane release of the juxtamembrane region in FGFR32014

    • Author(s)
      Hiroko Tamagaki, Yusuke Furukawa, Ritsuko Yamaguchi, Hironobu Hojo, Saburo Aimoto, Steven O. Smith and Takeshi Sato
    • Journal Title

      Biochemistry

      Volume: 53 Issue: 30 Pages: 5000-5007

    • DOI

      10.1021/bi500327q

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rational Design and Identification of Non-Peptidic Aggregation Inhibitor of Amyloid- Based on a Pharmacophore Motif Obtained from cyclo[-Lys-Leu-Val-Phe-Phe-].2014

    • Author(s)
      Tadamasa Arai, Takushi Araya, Daisuke Sasaki, Atsuhiko Taniguchi, Takeshi Sato, Youhei Sohma, and Motomu Kanai
    • Journal Title

      Angew. Chem. Int. Ed

      Volume: 53 Issue: 31 Pages: 8236-8239

    • DOI

      10.1002/anie.201405109

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Structural Characterization of the Transmembrane-Intracellular Juxtamembrane Region of FGFR3 and Its Implication in the Activation Mechanism2014

    • Author(s)
      Hiroko Tamagaki, Ritsuko Yamaguchi and Takeshi Sato
    • Journal Title

      Peptide Science 2013

      Volume: 2013 Pages: 59-60

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro reconstitution of a cellular like environment using liposome for Aβ peptide aggregation, its propagation, peptide-lipid interaction and drug screening2014

    • Author(s)
      Abhijit Saha,Goutam Mondal, Takeshi Sato and Surajit Ghosh
    • Journal Title

      Peptide Science 2013

      Volume: 2013 Pages: 109-110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transmembrane helix orientation influences membrane binding of the intracellular juxtamembrane domain in Neu receptor peptides2013

    • Author(s)
      Chihiro Matsushita, Hiroko Tamagaki, Yudai Miyazawa, Saburo Aimoto, Steven O. Smith and Takeshi Sato
    • Journal Title

      Proc. Natl. Acad. Sci.USA,

      Volume: 110 Pages: 1646-1651

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Tryptophan at the Transmembrane-Cytosolic Junction Modulates Thrombopoietin Receptor Dimerization and Activation2013

    • Author(s)
      Jean-Philippe Defour, Miki Itaya, Vitalina Gryshkova, Ian C. Brett, Christian Pecquet, Takeshi Sato, Steven O. Smith and Stefan N. Constantinescu
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 110 Issue: 7 Pages: 2540-2545

    • DOI

      10.1073/pnas.1211560110

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structure of the transmembrane and the intacelllular juxtamembrane of FGFR3 in lipid bilayers2013

    • Author(s)
      Hiroko Tamagaki, Saburo Aimoto and Takeshi Sato
    • Journal Title

      Peptide Science 2012

      Pages: 325-326

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of the intracellular juxtamembrane region with lipid bilayersdepends on relative orientation of transmembrane regions 1n dimer forreceptor tyrosine kinase2013

    • Author(s)
      Chihiro Matsushita, Hiroko Tamagaki, Saburo Aimoto, Steven O. Smith and Takeshi Sato
    • Journal Title

      Peptide Science 2012

      Pages: 327-328

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 受容体型チロシンキナーゼの膜貫通―膜近傍部位の構造機能解析2016

    • Author(s)
      佐藤 毅
    • Organizer
      蛋白研セミナー
    • Place of Presentation
      ホテル阪急エキスポパーク(大阪府吹田市)
    • Year and Date
      2016-03-03
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Research on structure and function of membrane protein using synthetic transmembrane peptides2015

    • Author(s)
      Takeshi Sato
    • Organizer
      19th Korean Peptide Protein Symposium
    • Place of Presentation
      Choongchungnam(韓国)
    • Year and Date
      2015-07-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 合成ペプチドを用いた1回膜貫通型タンパク質の構造機能解析2015

    • Author(s)
      佐藤 毅
    • Organizer
      第15回日本蛋白質科学会年会ワークショップ「生体膜上における事象の分子機構解明を目指すペプチド生命科学」
    • Place of Presentation
      徳島 あわぎんホール(徳島県徳島市)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] EGFR膜貫通-膜近傍部位の構造機能解析2014

    • Author(s)
      佐藤 毅
    • Organizer
      第87回日本生化学会, 京都2014. フォーラム「次世代脂質生物学を支える革新的テクノロジー」
    • Place of Presentation
      京都国際会館
    • Year and Date
      2014-10-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Mechanism for signaling through the membrane in activation of receptor tyrosine kinase; Molecular Targets for Diseases and Structural Life Science2014

    • Author(s)
      Takeshi Sato
    • Organizer
      The 9th International Symposium of the Institute Network
    • Place of Presentation
      大阪大学
    • Year and Date
      2014-06-19 – 2014-06-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ペプチド化学を基盤とした受容体チロシンキナーゼ膜貫通-膜近傍部位の構造機能解析2014

    • Author(s)
      佐藤 毅
    • Organizer
      生命分子機能研究会セミナー2014
    • Place of Presentation
      滋賀県長浜市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Structural biology on membrane protein using synthetic transmembrane peptides2013

    • Author(s)
      佐藤毅
    • Organizer
      4th Indian Peptide Symposium
    • Place of Presentation
      Saha Institute of Nuclear Physics (インド・コルカ(招待講演)
    • Year and Date
      2013-02-22
    • Related Report
      2012 Annual Research Report
  • [Presentation] Structural change in the transmembrane-juxtamembrane region of receptor tyrosine kinase for its activation2013

    • Author(s)
      Takeshi Sato
    • Organizer
      Membrane Protein Folding organized by the Biophysical Society (US) and the Korean Institute for Advanced Study
    • Place of Presentation
      Seoul, South Korea
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Structural Characterization of the Transmembrane-Intracellular Juxtamembrane Region of FGFR3 and Its Implication in the Activation Mechanism2013

    • Author(s)
      Hiroko Tamagaki, Ritsuko Yamaguchi and Takeshi Sato
    • Organizer
      第50回日本ペプチド討論会・第4回アジア太平洋国際ペプチド学会
    • Place of Presentation
      大阪府吹田市
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vitro reconstitution of a cellular like environment using liposome for Aβ peptide aggregation, its propagation, peptide-lipid interaction and drug screening2013

    • Author(s)
      Abhijit Saha,Goutam Mondal, Takeshi Sato and Surajit Ghosh
    • Organizer
      第50回日本ペプチド討論会・第4回アジア太平洋国際ペプチド学会
    • Place of Presentation
      大阪府吹田市
    • Related Report
      2013 Annual Research Report
  • [Presentation] EGF受容体ファミリーの活性化機構における膜貫通-細胞質内膜近傍部位の機能の解析2013

    • Author(s)
      松下千紘, 玉垣裕子, 相本三郎, Steven O. Smith, 佐藤 毅
    • Organizer
      第86回日本生化学会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 繊維芽細胞増殖因子受容体3の膜貫通-膜近傍部位の機能構造解析2013

    • Author(s)
      玉垣裕子, 相本三郎, 佐藤 毅
    • Organizer
      第86回日本生化学会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 受容体型チロシンキナーゼの二量体構造に依存する細胞質内膜近傍部位と脂質二重膜の相互作用の解析2012

    • Author(s)
      松下千紘, 玉垣裕子, 相本三郎,
    • Organizer
      第49回ペプチド討論会
    • Place of Presentation
      鹿児島県民交流センター(鹿児島市)
    • Year and Date
      2012-11-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] 繊維芽細胞増殖因子受容体(FGFR3)膜貫通一細胞質内膜近傍部位の脂質二重膜中における構造解析2012

    • Author(s)
      玉垣裕子, 相本三郎, 佐藤毅
    • Organizer
      第49回ペプチド討論会
    • Place of Presentation
      鹿児島県民交流センター(鹿児島市)
    • Year and Date
      2012-11-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] 一回膜貫通型蛋白質の半合成化学的調製2012

    • Author(s)
      玉垣裕子, 相本三郎, 佐藤毅
    • Organizer
      第12回日本蛋白質科学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2012-06-21
    • Related Report
      2012 Annual Research Report
  • [Presentation] 1回膜貫通型受容体活性化における膜貫通・膜近傍部位の機能解析2012

    • Author(s)
      佐藤毅, 玉垣裕子, 杣本三郎, Steven O. Smith
    • Organizer
      第12回日本蛋白質科学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2012-06-21
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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