Analysis of regulatory mechanisms for cell migration and cell polarity by Wnt5a and Ror2 receptor tyrosine kinase

• Project/Area Number: 19390076
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kobe University
• Principal Investigator: MINAMI Yasuhiro Kobe University, 大学院・医学研究科, 教授 (70229772)
• Co-Investigator(Kenkyū-buntansha): 依田 成玄 神戸大学, 大学院・医学系研究科, 助教 (70335454) ; 西田 満 神戸大学, 大学院・医学研究科, 准教授 (30379359) ; 寒川 延子 神戸大学, 大学院・医学系研究科, COE研究員 (30432579)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2008: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000); Fiscal Year 2007: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: Ror2受容体キナーゼ / Wnt5a / 細胞移動 / 細胞極性 / 細胞骨格 / Ror2受容体チロシンキナーゼ / 細胞骨格再編成 / 浸潤突起 / MMP13 / Srcファミリーチロシンキナーゼ / フィラミンA / JNK / シグナル伝達

Research Abstract

ヒトをはじめとする多細胞生物の形態形成過程において、複雑かつ精緻に制御された細胞移動・細胞極性が重要な役割を担っている。我々はRor2受容体チロシンキナーゼが、形態形成において重要な役割を担う分泌蛋白質Wnt5aの受容体として機能することを明らかにしていたが、本研究ではWnt5a/Ror2による細胞移動・細胞極性を調節する細胞内情報伝達機構の解析を行うとともに、この情報伝達機構の異常とがん等の病態との関連の解析を行った。

Research Products

• [Journal Article] Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2 (2008)
  • Author(s): Li, C., Chen, H., Hu, L., Xing, Y., Sasaki, T., Villosis, M. F., Li, J., Nishita, M., Minami, Y., and Minoo, P.
  • Journal Title: BMC Mol. Biol 9 Pages: 11-21
  • Peer Reviewed
• [Journal Article] Cthrcl selectively activates planar cell polarity pathway of Wnt signaling by stabilizing Wnt-receptor complex (2008)
  • Author(s): Yamamoto, S., Nishimura, O., Misaki, K., Nishita, M., Minami, Y., Yonemura, S., Tarui, H., and Sasaki, H.
  • Journal Title: Dev. Cell 15 Pages: 23-36
  • Peer Reviewed
• [Journal Article] Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A (2008)
  • Author(s): Nomachi, A., Nishita, M., Inaba, D., Enomoto, M., Hamasaki, M., and Minami, Y.
  • Journal Title: J. Biol. Chem 283 Pages: 27973-27981
  • Peer Reviewed
• [Journal Article] Wnt5a regulates directional cell migration and cell proliferation via the Ror2-mediated noncanonical pathway in mammalian palate development (2008)
  • Author(s): He, F., Xiong, W., Yu, X., Espinoza, R., Liu, C., Nishita, M., Yamada, G., Minami, Y., and Chen, Y.
  • Journal Title: Development 135 Pages: 3871-3879
  • Peer Reviewed
• [Journal Article] Arsenic Trioxide Augments Chk2/p53-mediated Apoptosis by Inhibiting Oncogenic Wipl Phosphatase. (2008)
  • Author(s): Minami Y.
  • Journal Title: J. Biol. Chem. 283 Pages: 18969-18979
  • Peer Reviewed
• [Journal Article] Cthrcl selectively activates the planar cell polarity pathway of Wnt signaling bystabilizing the Wnt-receptor complex (2008)
  • Author(s): Sasaki H.
  • Journal Title: Dev. Cell 15 Pages: 23-36
  • Peer Reviewed
• [Journal Article] Receptor tyrosine kinase Ror2 mediates Wnt5a-induced polarized cell migration by activating c-Jun N-terminal kinase via actin-binding protein filamin A. (2008)
  • Author(s): Minami Y.
  • Journal Title: J. Biol. Chem. 283 Pages: 27973-27981
  • Peer Reviewed
• [Journal Article] Ror2 modulates the canonical Wnt signaling in lung epithelialcells through cooperation with Fzd2. (2008)
  • Author(s): Li, C., Chen, H., Hu, L., Xing, Y., Sasaki, T., Villosis, M. F., Li, J., Nishita, M., Minami, Y., and Minoo, P.
  • Journal Title: BMC Mol. Biol. (in press)
  • Peer Reviewed
• [Journal Article] Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2 (2007)
  • Author(s): Yamamoto, H., Yoo S-K., Nishita, M., Kikuchi, A., and Minami, Y.
  • Journal Title: Genes Cells 12 Pages: 1215-1223
  • Peer Reviewed
• [Journal Article] A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-γ transactivation (2007)
  • Author(s): Takada, I., Mihara, M., Suzawa, M., Ohtake, F., Kobayashi, S., Igarashi, M., Youn, M-Y., Takeyama, K., Nakamura, T., Mezaki, Y., Takezawa, S., Yogiashi, Y., Kitagawa, H., Yamada, G., Takada, S., Minami, Y., Shibuya, H., Matsumoto, K., and Kato, S.
  • Journal Title: Nat. Cell Biol 9 Pages: 1273-1285
  • Peer Reviewed
• [Journal Article] Wnt5a modulates glycogen synthase kinase 3 to inducephosphorylation of receptor tyrosine kinase Ror2. (2007)
  • Author(s): Yamamoto, H., Yoo S-K., Nishita, M., Kikuchi, A., and Minami, Y.
  • Journal Title: Genes Cells 12 Pages: 1215-1223
  • Peer Reviewed
• [Journal Article] A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-γ transactivation. (2007)
  • Author(s): Takada, I., Mihara, M., Suzawa, M., Ohtake, F., Kobayashi, S., Igarashi, M., Youn, M-Y., Takeyama, K., Nakamura, T., Mezaki, Y., Takezawa, S., Yogiashi, Y., Kitagawa, H., Yamada, G., Takada, S., Minami, Y., Shibuya, H., Matsumoto, K., and Kato, S.
  • Journal Title: Nat. Cell Biol. 9 Pages: 1273-1285
  • Peer Reviewed
• [Presentation] Wnt5a/Ror2シグナルによる細胞運動制御 (2008)
  • Author(s): 西田 満, 南 康博
  • Organizer: 日本分子生物学会・日本生化学会合同年会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2008-12-12
• [Presentation] Wnt5a/Ror2シグナルによる細胞運動制御 (2008)
  • Author(s): 西田満、南康博
  • Organizer: 日本分子生物学会年会・日本生化学学会大会合同大会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Ror2 regulates cytoskeletal rearrangements to mediate Wnt5a-induced polarized cell migration (2007)
  • Author(s): 西田満、南康博
  • Organizer: 日本分子生物学会年会・日本生化学学会大会合同大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Ror2 regulates cytoskeletal rearrangements to mediate Wnt5a-induced polarized cell migration (2007)
  • Author(s): 西田満、野町昭、濱崎真弓、榎本真宏、南康博
  • Organizer: 第30回日本分子生物学会年会第80回日本生化学学会大会合同大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Roles of receptor tyrosine kinase Ror2 in Wnt5a-induced non-canonical Wnt signaling (2007)
  • Author(s): 南康博、兪史幹、菊池章、西田満
  • Organizer: The Wnt meeting in La Jolla
  • Place of Presentation: San Diego, U. S. A.
• [Presentation] Ror2 Regulatates Cytoskeletal Rearraangements to Mediate Wnt5a-induced Polarized Cell Migration. (2007)
  • Author(s): 野町昭、西田満、榎本真宏、濱崎真弓、南康博
  • Organizer: アメリカ細胞生物学会
  • Place of Presentation: Washington D. C., U. S. A.
• [Book] 受容体型チロシンキナーゼRor2によるWntシグナルの制御 : 実験医学、26巻15号(増刊) (2008)
  • Author(s): 西田満、南康博
• [Book] イラストレイテッド生化学原著4版Lippincott's Illustrated Reviews : Biochemistry 4th ed (2008)
  • Author(s): 西田満、依田成玄、南康博(石崎泰樹、丸山敬 監訳)
  • Total Pages: 619
  • Publisher: 丸善(株)出版
• [Book] イラストレイテッド生化学(原著4版) (2008)
  • Author(s): 石崎 泰樹
  • Total Pages: 619
  • Publisher: 丸善出版社
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/medzoo/
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/medzoo/
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/medzoo/