Functional analysis of a novel type of G protein-coupled receptor

• Project/Area Number: 19370055
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: ITOH Horoshi Nara Institute of Science and Technology, バイオサイエンス研究科, 教授 (10183005)
• Co-Investigator(Kenkyū-buntansha): MIZINO Norikazu 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (90212232) ; TAGO Kenji 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (20306111)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2008: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000); Fiscal Year 2007: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
• Keywords: 細胞情報伝達機構 / 受容体 / Gタンパク質 / シグナル伝達 / 生体分子 / 薬理学 / G蛋白質共役受容体

Research Abstract

Gタンパク質共役受容体(G protein-coupled receptor, GPCR)の中には、そのリガンドが不明のオーファン受容体が未だ数多く存在する. Adhesion GPCR に属するGPR56もオーファン受容体であり、ヒト大脳皮質形成および細胞のがん化に関与することが示唆されているが、その機能やシグナル伝達はほとんど不明であり、その解析を行った. その結果、アゴニスト様に働く抗GPR56抗体の作成に成功し、その抗体を用いてGPR56がGタンパク質のG12/13からRhoを介する経路を活性化して、神経前駆細胞の遊走に対して抑制的に働くことを明らかとした.

Research Products

• [Journal Article] G-protein signalling negatively regulates the stability of aryl hydrocarbon receptor (2009)
  • Author(s): Nakata A, Urano D, Fujii-Kuriyama Y, Mizuno N, Tago K, and Itoh H
  • Journal Title: EMBO Rep 10 Pages: 622-628
  • Peer Reviewed
• [Journal Article] Functions and regulatory mechanisms of Gq-signaling pathways (2009)
  • Author(s): Mizuno N, and Itoh H
  • Journal Title: Neurosignals 17 Pages: 42-54
  • Peer Reviewed
• [Journal Article] Functions and regulatory mechanisms of Gq-signaling pathways (2009)
  • Author(s): N. Mizuno
  • Journal Title: Neurosignals 17 Pages: 42-54
  • Peer Reviewed
• [Journal Article] G-protein signal 1 ing negat ively regulates the stability of arylhydrocarbon receptor (2009)
  • Author(s): A. Nakata
  • Journal Title: EMBO Reports in press
  • Peer Reviewed
• [Journal Article] Celecoxib potently inhibits TNFα-induced nuclear translocation and activation of NF-kB (2008)
  • Author(s): Funakoshi-Tago M, Shimizu T, Tago K, Nakamura M, Itoh H, Sonoda Y, and Kasahara T
  • Journal Title: Biochem Pharmacol 76 Pages: 662-671
  • Peer Reviewed
• [Journal Article] Domain-domain interaction of P-Rex1 is essential for the activation and inhibition by G protein βγ subunits and PKA (2008)
  • Author(s): Urano D, Nakata A, Mizuno N, Tago K, and Itoh H
  • Journal Title: Cell Signal 20 Pages: 1545-1554
  • Peer Reviewed
• [Journal Article] Orphan G proteincoupled receptor GPR56 regulates neural progenitor cell migration via a Gα12/13 and Rho pathway (2008)
  • Author(s): Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, and Itoh H
  • Journal Title: J Biol Chem 283 Pages: 14469-14478
  • Peer Reviewed
• [Journal Article] Heterotrimeric G protein (2008)
  • Author(s): Urano D, and Itoh H
  • Journal Title: Nippon Yakurigaku Zasshi 132 Pages: 121-123
  • NAID: 10024383659
  • Peer Reviewed
• [Journal Article] Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a Galpha 12/13 and Rho pathway (2008)
  • Author(s): T. Iguchi
  • Journal Title: J. Biol. Chem. 283 Pages: 14469-14478
  • Peer Reviewed
• [Journal Article] Domain-domain interaction of P-Rexl is essential for theactivation and inhibition by G protein betagamma subuni ts and PKA (2008)
  • Author(s): D. Urano
  • Journal Title: Cell. Signal. 20 Pages: 1545-1554
  • Peer Reviewed
• [Journal Article] 3量体G蛋白質 (2008)
  • Author(s): 浦野大輔
  • Journal Title: 日本薬理学雑誌 132 Pages: 121-123
  • Peer Reviewed
• [Journal Article] Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a Galpha 12/13 and Rho pathway (2008)
  • Author(s): T. Iguchi
  • Journal Title: J. Biol. Chem. (in press)
  • Peer Reviewed
• [Journal Article] Domain-domain interaction of P-Rex1 is essential for the activation and inhibition by G protein betagamma subunits and PKA (2008)
  • Author(s): D. Urano
  • Journal Title: Cell. Signal. (in press)
  • Peer Reviewed
• [Journal Article] The lipid raft proteins flotillins/reggies interact with Gαq and are involved in Gq-mediated p38 mitogen-activated protein kinase activation through tyrosine kinase (2007)
  • Author(s): Sugawara Y, Nishii H, Takahashi T, Yamauchi J, Mizuno N, Tago K, and Itoh H
  • Journal Title: Cell Signal 19 Pages: 1301-1308
  • Peer Reviewed
• [Presentation] 3量体Gタンパク質を標的とした薬剤の作用機構 (2009)
  • Author(s): 伊東広
  • Organizer: 第9回日本蛋白質科学会年会
  • Place of Presentation: 熊本
  • Year and Date: 2009-06-22
• [Presentation] 神経前駆細胞の自己複製能および細胞増殖能におけるGPE56の機能解析 (2008)
  • Author(s): 永野孝典
  • Organizer: 第31回日本分子生物学会第82回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] 活性酸素産生を司るRac-GEFであるP-Rex1のPKAによる抑制機構 (2008)
  • Author(s): 浦野大輔、中田飛鳥、水野憲一、多胡憲治、伊東広
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Gタンパク質結合分子Ric-8BはGαsの分解を抑制しGsシグナルを正に制御する (2008)
  • Author(s): 永井裕介、西村明幸、多胡憲治、水野憲一、伊東広
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] NF-kBシグナルに対する哺乳動物の2種類のRic-8の作用 (2008)
  • Author(s): 加戸美奈、西村明幸、永井裕介、多胡憲治、水野憲一、伊東広
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] NF-kB活性化に対する低分子量GTP結合タンパク質kB-Rasの抑制機構 (2008)
  • Author(s): 向縄昌輝、多胡憲治、水野憲一、伊東広
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] G蛋白質結合分子Ric-8BはGasの分解を抑制しGsシグナルを正に制御する (2008)
  • Author(s): 永井裕介
  • Organizer: 第31回日本分子生物学会第82回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Dynamic subcellular localization of atypical small GTPase kappaB-Ras and its possible contribution to oncogenic signals (2007)
  • Author(s): Tago K, Tago-Funakoshi M, Mizuno N, Kasahara T, Tominaga S, Itoh H
  • Organizer: 第80回日本生化学会第30回日本分子生物学会合同年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Gタンパク質シグナルによるダイオキシン受容体シグナル抑制機構の解析 (2007)
  • Author(s): 中田飛鳥、浦野大輔、水野憲一、多胡憲治、伊東広
  • Organizer: 第80回日本生化学会第30回日本分子生物学会合同年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] GPR56 regulates neural progenitor cell migration through G12/13 and Rho (2007)
  • Author(s): Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H
  • Organizer: 第80回日本生化学会第30回日本分子生物学会合同年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Ric-8B, a novel heterotrimeric G protein-binding protein, regulates Gs protein levels via modulating the ubiquitinproteasome ubiquitinproteasome pathways (2007)
  • Author(s): Nagai Y, Nishimura A, Hayashi A, Tago K, Mizuno N, Itoh H
  • Organizer: 第80回日本生化学会第30回日本分子生物学会合同年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] GPR56はG12/13とRhoを介して神経幹細胞の遊走を制御する (2007)
  • Author(s): 猪口 徳一
  • Organizer: 第30回日本分子生物学会年会第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] GPR56 regulates Neuronal Progenitor Cell Migration through G12/13 and Rho Axis (2007)
  • Author(s): Tokuichi Iguchi
  • Organizer: The American Society for Cell Biology 47th Annual Meeting
  • Place of Presentation: Washington, DC
  • Year and Date: 2007-12-02
• [Presentation] GPR56 Regulates Neural Progenitor Cell Migration through G12/13 and Rho Axis (2007)
  • Author(s): Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H
  • Organizer: 47th Annual Meeting of the American Society for Cell Biology
  • Place of Presentation: Washington DC
  • Year and Date: 2007-11-22
• [Presentation] A novel type of G protein inhibitor, YM-254890, acts as a Gq-specific guanine nucleotide dissociation inhibitor via the switch 1 region of Gα subunit (2007)
  • Author(s): Nishimura, A., Sugawara, Y., Takasaki, J., Taniguchi, M., Mizuno, N. and Itoh, H.
  • Organizer: Experimental Biology Annual Meeting
  • Place of Presentation: Washington DC
  • Year and Date: 2007-04-29
• [Book] 三量体Gタンパク質 (2008)
  • Author(s): 浦野 大輔
  • Publisher: 日本薬理学雑誌(in press)
• [Remarks]
  • URL: http://bsw3.naist.jp/itoh/home/index.html
• [Patent(Industrial Property Rights)] Gタンパク質共役受容体に対する機能抗体およびその応用 (2007)
  • Inventor(s): 伊東広、水野憲一、多胡憲治、猪口徳一、永野孝典
  • Industrial Property Rights Holder: 国立大学法人奈良先端科学技術大学院大学
  • Industrial Property Number: 2007-284829
  • Filing Date: 2007-11-01