Regulation of the endosomal sorting and intracellular signaling ofgrowth factor receptors

• Project/Area Number: 19370050
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: KITAMURA Naomi Tokyo Institute of Technology, 大学院・生命理工学研究科, 教授 (80107424)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000); Fiscal Year 2008: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2007: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
• Keywords: 細胞増殖因子受容体 / エンドソーム / 選別輸送 / シグナル伝達 / Hrs / ERK 経路 / 脱ユビキチン化酵素UBPY / ミオシン重鎖9 / ERK経路 / アダプター蛋白質Gab1 / CHMP4B / ERK

Research Abstract

細胞増殖因子受容体のエンドソームでの選別輸送とシグナル伝達の関係について、選別輸送制御因子であるHrsの過剰発現細胞およびUBPYの欠損マウスを用いて解析を行った結果、受容体の選別輸送の制御が受容体からのシグナル伝達に関わり細胞増殖制御に重要な役割を果たしていることが明らかになった。またHrsの結合蛋白質ミオシン重鎖9とUBPYの結合蛋白質CHMP4が、増殖因子受容体のエンドソームでの選別輸送を制御していることが明らかになった。

Research Products

• [Journal Article] Nucleolar structure andfunction are regulated by thedeubiquitinating enzyme USP36 (2009)
  • Author(s): A. Endo, M. Matsumoto, T. Inada, A.Yamamoto, K. I. Nakayama, N. Kitamura, and M. Komada
  • Journal Title: J. Cell Sci. 122 Pages: 678-686
  • Peer Reviewed
• [Journal Article] Nucleolar structure and function are regulated by the deubiquitinating enzyme USP36 (2009)
  • Author(s): A. Endo
  • Journal Title: J. Cell Sci. 122 Pages: 678-686
  • Peer Reviewed
• [Journal Article] Expression of CAR inSW480 and HepG2 cells during G1 associatedwith cell proliferation (2008)
  • Author(s): M. Osabe, J. Sugatani, A. Takemura, Y.Yamazaki, A. Ikari, N. Kitamura, M.Negishi, and M. Miwa
  • Journal Title: Biochem. Biophys.Res. Commun. 369 Pages: 1027-1033
  • Peer Reviewed
• [Journal Article] Dynamicregulation of ubiquitylation anddeubiquitylation at the central spindleduring cytokinesis (2008)
  • Author(s): A. Mukai, E. Mizuno, K. Kobayashi, A.Yamamoto, M. Matsumoto, K. Nakayama, N.Kitamura, and M. Komada
  • Journal Title: J. Cell Sci. 121 Pages: 1325-1333
  • Peer Reviewed
• [Journal Article] Coupling of Grb2 to Gab1 mediateshepatocyte growth factor-induced highintensity ERK signal required forinhibition of HepG2 hepatoma cellproliferation (2008)
  • Author(s): A. Kondo, N. Hirayama, Y. Sugito, M.Shono, T. Tanaka, and N. Kitamura
  • Journal Title: J. Biol. Chem. 283 Pages: 1428-1436
  • Peer Reviewed
• [Journal Article] Up-regulationof p21^<CIP1>expression mediated byERK-dependent and -independent pathwayscontributes to hepatocyte growthfactor-induced inhibition of HepG2hepatoma cell proliferation (2008)
  • Author(s): E. Shirako, N. Hirayama, Y. Tsukada,T. Tanaka, and N. Kitamura
  • Journal Title: J. Cell.Biochem. 104 Pages: 176-188
  • Peer Reviewed
• [Journal Article] 14-3-3-dependent inhibition of thedeubiquitinating activity of UBPY and itscancellation in the M phase (2008)
  • Author(s): E. Mizuno, N. Kitamura, and M. Komada
  • Journal Title: Exp. Cell Res. 313 Pages: 3624-3634
  • Peer Reviewed
• [Journal Article] Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis (2008)
  • Author(s): A. Mukai
  • Journal Title: J. Cell Sci. 121 Pages: 1325-1333
  • Peer Reviewed
• [Journal Article] Expression of CAR in SW480 and HepG2 cells during G1 associated with cell proliferation (2008)
  • Author(s): M. Osabe
  • Journal Title: Biochem. Biophys. Res. Commun. 369 Pages: 1027-1033
  • Peer Reviewed
• [Journal Article] Up-regulation of p21CIP1 expression mediated by ERK-dependent and independent pathways contributes to hepatocyte growth factor-induced inhibition of HepG2 hepatoma cell proliferation (2008)
  • Author(s): E. Shirako
  • Journal Title: J. Cell. Biochem (in press)
  • Peer Reviewed
• [Journal Article] Coupling of Grb2 to Gab1 mediates hepatocyte growth factor-induced high Intensity ERK signal required for inhibition of HepG2 hepatoma cell proliferation (2008)
  • Author(s): A. Kondo
  • Journal Title: J. Biol. Chem. 283 Pages: 1428-1436
  • Peer Reviewed
• [Journal Article] Id1 is downregulated byhepatocyte growth factor viaERK-dependent and-independent signalingpathways (2007)
  • Author(s): K. Ushio, T. Hashimoto, N. Kitamura,and T. Tanaka
  • Journal Title: leading to increased expressionof p16^<INK4a>in human hepatoma cells. Mol.Cancer Res. (in press)
  • Peer Reviewed
• [Journal Article] 14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase (2007)
  • Author(s): E. Mizuno
  • Journal Title: Exp. Cell Res. 313 Pages: 3624-3634
  • Peer Reviewed
• [Presentation] ツメガエル初期胚の尾部形成における母性CyclinE蛋白質分解によるエピジェネティックな制御 (2008)
  • Author(s): 田中利明、喜多村直実
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-12
• [Presentation] ツメガエル初期胚の尾部形成における母性CyclinE蛋白質分解によるエピジェネティックな制御 (2008)
  • Author(s): 田中 利明
  • Organizer: 日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-12
• [Presentation] 脱ユビキチン化酵素USP36による核小体機能の制御 (2008)
  • Author(s): 遠藤彬則、山本章嗣、松本雅記、中山敬一、稲田利文、喜多村直実、駒田雅之
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-11
• [Presentation] 重層扁平上皮における肝細胞増殖因子HGF刺激によるmicroRNA発現変化 (2008)
  • Author(s): 鈴木弟、長沼誠二、木村相泰、喜多村直実、藤枝重治、伊藤浩史
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-11
• [Presentation] HGF刺激による大腸癌細胞株の形態変化に関与するmiRNAの発現変動 (2008)
  • Author(s): 長沼誠二、鈴木弟、木村相泰、喜多村直実、伊藤浩史
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-11
• [Presentation] 脱ユビキチン化酵素USP36の機能解析 (2007)
  • Author(s): 遠藤彬則、喜多村直実、駒田雅之
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-14
• [Presentation] HAI-1標的模型プロテアーゼの探索 (2007)
  • Author(s): 橋本富男、加藤稔、福島剛、田中弘之、片岡寛章、喜多村直実、下村猛
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-13
• [Presentation] 肝癌細胞株HepG2における肝細胞増殖因子によるCdkインヒビターp16^<INK4a>の発現制御の分子機構 (2007)
  • Author(s): 潮和敬、喜多村直実、田中利明
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-11
• [Presentation] ツメガエル初期発生過程における母性CyclinE蛋白質の分解による形態形成の制御 (2007)
  • Author(s): 田中利明、喜多村直実
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-11
• [Remarks]
  • URL: http://www.kitamura-lab.bio.titech.ac.jp/