Function of the transmembrane-juxtamembrane region of receptor tyrosine kinase in its activity regulation

• Project/Area Number: 19710186
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Living organism molecular science
• Research Institution: Osaka University
• Principal Investigator: SATO Takeshi Osaka University, 蛋白質研究所, 助教 (90403013)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 活性発現の分子機構 / 受容体型チロシンキナーゼ / 固体NMR / 膜蛋白質 / ライゲーション

Research Abstract

本研究は細胞の発生や分化に重要な役割を果たしている受容体型チロシンキナーゼ,特に繊維芽細胞成長因子受容体(FGFR3)の活性化メカニズム,活性制御のメカニズムにおける膜貫通(TM)部位,細胞質内膜近傍(juxtamembrane :JM)部位の機能の解明を目的したものである. FGFR3のTM-JM部位配列の合成化学的調製法を確立し,その方法を用いて調製した試料を用いることにより, 当受容体TM-JM 配列の構造解析を行った. その結果,野生型の配列,常時活性型変異が導入されたそれら二つの配列ではdimerization interface,さらにはJM部位の構造が異なるという知見を得た. この結果はTM部位での構造変化が,JM部位にも影響を与え, 挙動の違いとして現れることを初めて示すものであり, 受容体型チロシンキナーゼの機能発現メカニズムの解明に大きく貢献するものと考えている.

Research Products

• [Journal Article] AHelix-to-Coil Transition at the ε -Cut Site in the Transmembrane Dimer of the Amyloid Precursor Protein is Required for Proteolysis (2009)
  • Author(s): Takeshi Sato, Tzu-chun Tang, Gabriella Reubins, Jeffrey Z. Fei, Taiki Fujimoto, Pascal Kienlen-Campard, Stefan N. Constantinescu, Jean-Noel Octave, Saburo Aimoto, Steven O. Smith.
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 1421-1426
  • Peer Reviewed
• [Journal Article] Structure of the Transmembrane (2009)
  • Author(s): Takeshi Sato, Tzu-chun Tang, Gabriella Reubins, Jeffrey Z. Fei, Taiki Fujimoto, Hiroko Tamagaki, Pascal Kienlen-Campard, Stefan N. Constantinescu, Jean-Noel Octave, Steven O. Smith and Saburo Aimoto
  • Journal Title: Juxtamembrane Region of Amyloid Peptide Science 2008 Pages: 89-90
  • Peer Reviewed
• [Journal Article] A Helix-to-Coil Transition at the ε-Cut Site in the Transmembrane Dimer of the Amyloid Precursor Protein is Required for Proteolysis (2009)
  • Author(s): Sato, Takeshi
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 1421-1426
  • Peer Reviewed
• [Journal Article] Jean-Noel Octave Amyloidogenic processing but not aicd production requires a precisely oriented APP dimer assembled by transmembrane GXXXG motifs (2008)
  • Author(s): Pascal Kienlen-Campard, Bernadette Tasiaux, Joanne Van Hees, Mingli Li, Sandra Huysseune, Takeshi Sato, Jeffrey. Z. Fei, Saburo Aimoto, Pierre J. Courtoy, Steven O. Smith, Stefan N.Constantinescu, Jean-Noel
  • Journal Title: J. Biol Chem. 283 Pages: 7733-7744
  • Peer Reviewed
• [Journal Article] Peptide Thioester Synthesis Based on an N-S Acyl Shift Reaction (2008)
  • Author(s): Ken'ichiroh Nakamura, Tomoya Uesugi, Takeshi Sato, Toru Kawakami, Saburo Aimoto
  • Journal Title: Peptide Science 2007 Pages: 41-42
  • NAID: 10021906551
  • Peer Reviewed
• [Journal Article] Chemical Synthesis of the Extracellular Juxtamembrane-Transmembrane Region of Thrombopoietin Receptor (2008)
  • Author(s): Tomoya Uesugi, Ken'ichiroh Nakamura, Takeshi Sato, Toru Kawakami and Saburo Aimoto
  • Journal Title: Peptide Science 2007 Pages: 211-212
  • NAID: 10021906895
  • Peer Reviewed
• [Journal Article] Structural Analysis of the Transmembrane-Juxtamembrane Region of FGFR3 (2008)
  • Author(s): Yusuke Furukawa, Takeshi Sato, Chihiro Matsushita, Yuen H. Lam, Xin Zhao, Steven O. Smith and Saburo Aimoto
  • Journal Title: Peptide Science 2007 Pages: 319-320
  • NAID: 10021907085
  • Peer Reviewed
• [Journal Article] Structure of the Membrane Reconstituted Transmembrane-Juxtamembrane Peptide Neu(647-693) and Its Interaction with Ca2+/Calmodulin (2008)
  • Author(s): Chihiro Matsushita, Takeshi Sato, Yusuke Furukawa, Yuen Han Lam, Xin Zhao, Steven O. Smith, Saburo Aimoto
  • Journal Title: Peptide Science 2007 Pages: 501-502
  • NAID: 10021907427
  • Peer Reviewed
• [Journal Article] Amyloidogenic processing but not AICD production requires a precisely oriented APP dimer assembled by transmembrane GXXXGmotifs (2008)
  • Author(s): Pascal Kienlen-Campard
  • Journal Title: J.Biol.Chem. (印刷中)
  • Peer Reviewed
• [Journal Article] Peptide Thioester Synthesis Basedon an N-S Acyl Shift Reaction (2008)
  • Author(s): Ken'ichiroh Nakamura
  • Journal Title: Peptide Sience 2008 (印刷中)
  • Peer Reviewed
• [Journal Article] Chemical Synthesis of the Extracellular Juxtamembrane-Transmembrane Region of Thrombopoietin Receptor (2008)
  • Author(s): Tomoya Uesugi
  • Journal Title: Peptide Sience 2008 (印刷中)
  • Peer Reviewed
• [Journal Article] Structual Analysis of the Transmembrane-Juxtamembrane Region of FGFR3 (2008)
  • Author(s): Yusuke Furukawa
  • Journal Title: Peptide Sience 2008 (印刷中)
  • Peer Reviewed
• [Journal Article] Structure of the Menbrane Reconstituted Transmembrane-Juxtamembrane Peptode Neu(647-693) and Its Interaction with Ca^<2+>/Calmodulin (2008)
  • Author(s): Chihiro Matsushita
  • Journal Title: Peptide Sience 2008 (印刷中)
  • Peer Reviewed
• [Journal Article] Peptide purification by affinity chromatography based on α-ketoacyl group chemistry
  • Author(s): Toshiaki Hara, Akira Tainosho, Ken'ichiroh Nakamura, Takeshi Sato, Toru Kawakami, Saburo Aimoto
  • Journal Title: J. Pept. Sci (in press)
  • Peer Reviewed
• [Journal Article] High resolution 1H MAS RFDR NMR of biological membranes
  • Author(s): Darryl Aucoin, Devin Camenares, Xin Zhao, Jay Jung, Takeshi Sato and Steven O. Smith
  • Journal Title: J. Mag.Reson. (in press)
  • Peer Reviewed
• [Journal Article] Peptide purification by affinity chromatography based on α-ketoacyl group chemistry
  • Author(s): Hara. Toshiaki
  • Journal Title: J. Pept. Sci. (印刷中)
  • Peer Reviewed
• [Journal Article] High resolution 1H MAS RFDR NMR of biological membranes
  • Author(s): Aucoin, Darryl
  • Journal Title: J Mag. Reson. (印刷中)
  • Peer Reviewed
• [Presentation] Structure of the transmembrane-juxtamembrane region of the amyloid precursor protein : Implication for proteolysis at the ε-cut site (2009)
  • Author(s): Takeshi Sato, Steven O. Smith, Saburo Aimoto
  • Organizer: Life Science against Intractable Diseases, The joint Symposium of the 4th International Symposium of Institutes Network and Osaka University Global COE Symposium
  • Place of Presentation: Hotel Hankyu Expo Park
• [Presentation] Structure of the transmembrane-juxtamembrane region of the amyloid precursor protein : Implication for proteolvsis at the ε-cut site (2009)
  • Author(s): Sato, Takeshi
  • Organizer: Life Science against Intractable Diseases, The joint Symposium of the 4th International Symposium of Institutes Network and Osaka University Global COE Symposium
  • Place of Presentation: Hotel Hankyu Expo Park吹田
• [Presentation] Structure of the transmembrane-juxtamembrane region of single transmembrane proteins (2008)
  • Author(s): Sato, Takeshi
  • Organizer: The 7th OIB Symposium
  • Place of Presentation: 岡崎カンファレンスセンター、岡崎
  • Year and Date: 2008-11-13
• [Presentation] Structure of the transmembrane-juxtamembrane region of single transmembrane proteins (2008)
  • Author(s): Takeshi Sato, Steven O. Smith, Saburo Aimoto
  • Organizer: The 7th OIB Symposium
  • Place of Presentation: 岡崎カンファレンスセンター, 岡崎
• [Presentation] Structure of the Transmembrane - Juxtamembrane Region of Amyloid Precursor Protein (2008)
  • Author(s): Takeshi Sato, Tzu-chun Tang, Gabriella Reubins, Jeffrey Z. Fei, Taiki Fujimoto, Hiroko Tamagaki, Pascal Kienlen-Campard, Stefan N. Constantinescu, Jean-Noel Octave, Steven O. Smith and Saburo Aimoto
  • Organizer: 第45 回日本ぺプチド討論会
  • Place of Presentation: 2008 タワーホール船堀
• [Presentation] Structural studies on the membrane reconstituted transmembrane-juxtamembrane region of ErbB2/Neu (2008)
  • Author(s): Chihiro Matsushita, Takeshi Sato, Yusuke Furukawa, Yuen Han Lam, Xin Zhao, Steven O. Smith and Saburo Aimoto
  • Organizer: 30th European Peptide Symposium
  • Place of Presentation: Finlandia Hall, Helsinki, Finland
• [Presentation] FGFR3膜貫通-細胞質内膜近傍部位の構造解析 (2008)
  • Author(s): 佐藤毅, 古川祐輔, 松下千紘, Steven O. Smith, 相本三郎
  • Organizer: 第8回日本蛋白質科学会年会
  • Place of Presentation: タワーホール船堀
• [Presentation] Structural studies on the membrane reconstituted transmembrane-juxtamembrane region of ErbB2/Neu (2008)
  • Author(s): Matsushita, Chihiro
  • Organizer: European Peptide Symposium
  • Place of Presentation: Finlandia Hall, Helsinki, Finland
• [Presentation] ErbB2/Neuの膜貫通-細胞質内膜近傍部位の構造解析 (2008)
  • Author(s): 松下千紘
  • Organizer: 第8回日本蛋白質科学会年会
  • Place of Presentation: タワーホール船堀
• [Presentation] Structure of the transmembrane and juxtamembran e region of Neu and FGFR3 (2007)
  • Author(s): Takeshi Sato
  • Organizer: 第30回日本分子生物学会/第80回日本生化学会 合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Structural Analysis of the Transmembrane-Juxtarnembrane Regien of FGFR3 (2007)
  • Author(s): Takeshi Sato
  • Organizer: 第44回日本ペプチド討論会
  • Place of Presentation: 富山
  • Year and Date: 2007-11-07
• [Presentation] Peptide Thioester Synthesis Basedon an N-S Acy1 Shift Reaction (2007)
  • Author(s): Ken'ichiroh Nakamura
  • Organizer: 第44回目本ペプチド討論会
  • Place of Presentation: 富山
  • Year and Date: 2007-11-06
• [Presentation] Chemical Synthesis of the Extracellular Juxtamembrane-Transmembrane Region of Thrombopoietin Receptor (2007)
  • Author(s): Takeshi Sato
  • Organizer: 第44回日本ペプチド討論会
  • Place of Presentation: 富山
  • Year and Date: 2007-11-06
• [Presentation] Structure of the Membrane Reconstituted Transmembiane-Juxtainembiane P eptide Neu(647-693) arid lts Interaction with Ca^<2+>/Calmodulin (2007)
  • Author(s): Takeshi Sato
  • Organizer: 第44回日本ペプチド討論会
  • Place of Presentation: 富山
  • Year and Date: 2007-11-06
• [Presentation] ネイティブケミカルラィゲーショシ法によるFGFR3膜貫通一膜近傍部位ベプチドの化学合成 (2007)
  • Author(s): 佐藤 毅
  • Organizer: 第7回日本蛋白質科学会年会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-25
• [Presentation] Structure of the transmembrane and juxtamembrane region of Neu and FGFR3 (2007)
  • Author(s): Takeshi Sato, Yusuke Furukawa, Chihiro Matsushita, Steven O. Smith, Saburo Aimoto
  • Organizer: 第30回日本分子生物学会/第80回日本生化学会 合同大会
  • Place of Presentation: パシフィコ横浜、ヨコハマグランドイインターコンチネンタルホテル横浜
• [Presentation] Peptide Thioester Synthesis Based on an N-S Acyl Shift Reaction (2007)
  • Author(s): Ken'ichiroh Nakamura, Tomoya Uesugi,Takeshi Sato, Toru Kawakami, Saburo Aimoto
  • Organizer: 第44回日本ぺプチド討論会2007
  • Place of Presentation: 富山国際会議場 富山
• [Presentation] Chemical Synthesis of the Extracellular Juxtamembrane-Transmembrane Region of Thrombopoietin Receptor (2007)
  • Author(s): Tomoya Uesugi, Ken'ichiroh Nakamura, Takeshi Sato, Toru Kawakami, Saburo Aimoto
  • Organizer: 第44回日本ぺプチド討論会2007
  • Place of Presentation: 富山国際会議場 富山
• [Presentation] Structural Analysis of the Transmembrane-Juxtamembrane Region of FGFR3 (2007)
  • Author(s): Yusuke Furukawa, Takeshi Sato, Chihiro Matsushita, Yuen H. Lam, Xin Zhao, Steven O. Smith, Saburo Aimoto
  • Organizer: 第44回日本ぺプチド討論会2007
  • Place of Presentation: 富山国際会議場 富山
• [Presentation] Structure of the Membrane Reconstituted Transmembrane-Juxtamembrane Peptide Neu(647-693) and Its Interaction with Ca2+/Calmodulin (2007)
  • Author(s): Chihiro Matsushita, Takeshi Sato, Yusuke Furukawa, Yuen Han Lam, Xin Zhao, Steven O. Smith and Saburo Aimoto
  • Organizer: 第44回日本ぺプチド討論会2007
  • Place of Presentation: 富山国際会議場 富山
• [Presentation] ネイティブケミカルライゲーション法によるFGFR3膜貫通-膜近傍部位ぺプチドの化学合成 (2007)
  • Author(s): 古川祐輔, 佐藤毅, Steven O. Smith, 相本三郎
  • Organizer: 第7回日本蛋白質科学会年会
  • Place of Presentation: 仙台