Functional analyses of receptor tyrosine kinases, Ror1 and Ror2, in Wnt signalin

• Project/Area Number: 21390080
• 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 神戸大学, 大学院・医学研究科, 教授 (70229772)
• Co-Investigator(Kenkyū-buntansha): NISHITA Michiru 神戸大学, 大学院・医学研究科, 准教授 (30379359) ; 遠藤 光晴 神戸大学, 医学研究科, 助教 (90436444)
• Co-Investigator(Renkei-kenkyūsha): ENDO Mitsuharu 神戸大学, 大学院・医学研究科, 助教 (90436444)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2011: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2009: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: Wnt5a / Ror1 / Ror2 / 癌の浸潤 / 神経細胞分化 / Wntシグナル / MMP / 神経幹細胞性維持 / Dishevelled / Wntシグナル伝達 / チロシンキナーゼ / マトリックスメタロプロテアーゼ

Research Abstract

In mammals, including humans, binding of an secreted protein, Wnt5a, to its cognate receptors, the receptor tyrosine kinases, Ror1 and Ror2, elicits intracellular signalings that play important roles in the morphogenesis of tissues and organs during the developmental processes. In this study, we have shown that Wnt5a-Ror1/Wnt5a-Ror2 signalings play important roles in the morphogenesis of tissues and organs by regulating cell polarity and migration, and have elucidated the relationship between abnormalities in these signalings and developmental anomalies and cancer invasion.

Research Products

• [Journal Article] Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex (2012)
  • Author(s): Endo, M., Doi, R., Nishita, M., Minami, Y.
  • Journal Title: J. Cell Sci Volume: (in press)
• [Journal Article] Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis (2012)
  • Author(s): Maeda, K., Kobayashi, Y., Udagawa, N., (省略7名), Nishita, M., Marumo, K., Martin, T. J., Minami, Y., Takahashi, N.
  • Journal Title: Nat. Med Volume: 18 Pages: 405-412
• [Journal Article] Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase(MMP)-13 expression (2012)
  • Author(s): Yamagata, K., Li, X., Ikegaki, S., Oneyama, C., Okada, M., Nishita, M., Minami, Y.
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 1588-1599
• [Journal Article] Analysis of Wnt/Planar cell polarity pathway in cultured cells (2012)
  • Author(s): Endo, M., Nishita, M., Minami, Y.
  • Journal Title: Methods Mol. Biol Volume: 839 Pages: 201-214
• [Journal Article] Analysis of Wnt/Planar cell polarity pathway in cultured cells (2012)
  • Author(s): Endo, M., Nishita, M., Minami, Y.
  • Journal Title: Methods Mol.Biol. Volume: 839 Pages: 201-214
• [Journal Article] Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP)-13 expression (2012)
  • Author(s): Yamagata, K., Li, X., Ikegaki, S., Oneyama, C., Okada, M., Nishita, M., Minami, Y.
  • Journal Title: J.Biol.Chem. Volume: 287 Pages: 1588-1599
  • Peer Reviewed
• [Journal Article] Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex (2012)
  • Author(s): Endo, M., Doi, R., Nishita, M., Minami, Y.
  • Journal Title: J.Cell Sci. Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis (2012)
  • Author(s): Maeda, K., Kobayashi, Y., Udagawa, N., Uehara, S., Ishihara, A., Mizoguchi, T., Kikuchi, Y., Takada, I., Kato, S., Kani, S., Nishita, M., Marumo, K., Martin, T.J., Minami, Y., Takahashi, N.
  • Journal Title: Nat.Med. Volume: (印刷中) Issue: 3 Pages: 405-12
  • DOI: 10.1038/nm.2653
  • Peer Reviewed
• [Journal Article] Critical role of Wnt5a-Ror2 signaling in motility and invasiveness of epidermoid carcinoma cells following Snail-mediated epithelial-mesenchymal transition (2011)
  • Author(s): Ren, D., Minami, Y., Nishita, M.
  • Journal Title: Genes Cells Volume: 16 Pages: 304-315
• [Journal Article] Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2 (2011)
  • Author(s): Gao, B., Song, H., (省略7名), Minami, Y., Economedes, A. N., Yang, Y.
  • Journal Title: Dev. Cell Volume: 20 Pages: 163-176
• [Journal Article] Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2 (2011)
  • Author(s): Gao, B., Song, H., Bishop, K., Eliott, G., Garrett, L., English, M.A., Andre, P., Robinson, J., Sood, R., Minami, Y., Economedes, A.N., Yang, Y.
  • Journal Title: Dev.Cell Volume: 20 Pages: 163-176
  • Peer Reviewed
• [Journal Article] Non-canonical Wnt signaling mediates androgen-dependent tumor growth in a mouse model of prostate cancer (2011)
  • Author(s): Takahashi, S., Watanabe, T., Okada, M., Inoue, K., Ueda, T., Takada, I., Watabe, T., Yamamoto, Y., Fukuda, T., Nakamura, T., Akimoto, C., T., Fujimura, T., Hoshino, M., Imai, Y., Metzger, D., Miyazono, K., Minami, Y., Chambon, P., Kitamura, T., Matsumoto, T., Kato, S.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 108 Pages: 4938-4943
  • Peer Reviewed
• [Journal Article] Critical role of Wnt5a-Ror2 signaling in motility and invasiveness of epidermoid carcinoma cells following Snail-mediated epithelial-mesenchymal transition. (2011)
  • Author(s): Ren, D., et al.
  • Journal Title: Genes Cells Volume: 16 Pages: 304-315
  • Peer Reviewed
• [Journal Article] Wnt signaling gradients establish planar cell polarity by inducing Vangl2 phosphorylation through Ror2. (2011)
  • Author(s): Gao, B., et al.
  • Journal Title: Dev.Cell Volume: 20 Pages: 163-176
  • Peer Reviewed
• [Journal Article] Mice lacking the orphan receptor Ror1 have distinct skeletal abnormalities and are growth retarded (2010)
  • Author(s): Lyashenko, N., Weissenbock, M., Sharir, A., Erben, R. G., Minami, Y., Hartmann, C.
  • Journal Title: Dev. Dyn Volume: 239 Pages: 2266-2277
• [Journal Article] Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization (2010)
  • Author(s): Nishita, M., Itsukushima, S., Nomachi, A., Endo, M., Wang, Z-C., Inaba, D., Qiao, S., Takada, S., Kikuchi, A., Minami, Y.
  • Journal Title: Mol. Cell. Biol Volume: 30 Pages: 3610-3619
• [Journal Article] Cell/tissue-tropic functions of Wnt5a signaling in normal and cancer cells (2010)
  • Author(s): Nishita, M., Enomoto, M., Yamagata, K. Minami, Y.
  • Journal Title: Trends in Cell Biol Volume: 20 Pages: 346-354
• [Journal Article] Ror2 is required for midgut elongation during mouse development (2010)
  • Author(s): Yamada, M., Udagawa, J., Matsumoto, A., Hashimoto, R., Nishita, M., Minami, Y., Otani, H.
  • Journal Title: Dev. Dyn Volume: 239 Pages: 941-953
• [Journal Article] The Ror-family receptor tyrosine kinases in non-canonical Wnt signaling : Their implications in developmental morphogenesis and human diseases (2010)
  • Author(s): Minami, Y., Oishi, I., Endo, M., Nishita, M.
  • Journal Title: Dev. Dyn Volume: 239 Pages: 1-15
• [Journal Article] Cell/tissue-tropic function of Wnt5a signaling in normal and cancer cells. (2010)
  • Author(s): Nishita, M., et al.
  • Journal Title: Trends in Cell Biol. Volume: 20 Pages: 346-354
  • Peer Reviewed
• [Journal Article] Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulsting Dishevelled polymerization. (2010)
  • Author(s): Nishita, M., et al.
  • Journal Title: Mol.Cell.Biol. Volume: 30 Pages: 3610-3619
  • Peer Reviewed
• [Journal Article] Filamin associates with stress signaling kinase MKK7 and MKK4 and regulates JNK activation. (2010)
  • Author(s): Nakagawa, K., et al.
  • Journal Title: Biochem.J. Volume: 427 Pages: 237-245
  • Peer Reviewed
• [Journal Article] Mice lacking the orphan receptor Rorl have distinct skeletal abnormalities and are growth retarded. (2010)
  • Author(s): Lyashenko, N., et al.
  • Journal Title: Dev.Dyn. Volume: 239 Pages: 2266-2277
  • Peer Reviewed
• [Journal Article] Ror2 is required for midgut elongation during mouse development (2010)
  • Author(s): Yamada, M., et al.
  • Journal Title: Dev.Dyn. 239 Pages: 941-953
  • Peer Reviewed
• [Journal Article] The Ror-family receptor tyrosine kinases in non-canonical Wnt signaling : Their implications in developmental morphogenesis and human diseases (2010)
  • Author(s): Minami, Y., et al.
  • Journal Title: Dev.Dyn. 239 Pages: 1-15
  • Peer Reviewed
• [Journal Article] Filamin associates with stress signaling kinase MKK7 and MKK4 and regulates JNK activation (2010)
  • Author(s): Nakagawa, K., et al.
  • Journal Title: Biochem.J. (in press)
  • Peer Reviewed
• [Journal Article] The Ror2 receptor requires tyrosine kinase activity to mediate Wnt5a signaling (2009)
  • Author(s): Mikels, A., Minami, Y., Nusse, R.
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 30167-30176
• [Journal Article] Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling (2009)
  • Author(s): Enomoto, M., Hayakawa, S., Itsukushima, S., Dayong, R., Matsuo, M., Tamada, K., Oneyama, C., Okada, M., Takumi, T., Nishita, M., Minami, Y.
  • Journal Title: Oncogene Volume: 28 Pages: 3197-3208
• [Journal Article] Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling (2009)
  • Author(s): Enomoto, M., et al.
  • Journal Title: Oncogene 28 Pages: 3197-3208
  • Peer Reviewed
• [Journal Article] The Ror2 receptor requires tyrosine kinase activity to mediate Wnt5a signaling (2009)
  • Author(s): Mikels, A., et al.
  • Journal Title: J.Biol.Chem 284 Pages: 30167-30176
  • Peer Reviewed
• [Journal Article] Ror2 expression in squamous cell carcinoma and epithelial dysplasia of the oral cavity (2009)
  • Author(s): Kobayashi, M., et al.
  • Journal Title: Oral Surg.Oral Med.Oral Pathol.Oral Radiol.Endod 107 Pages: 398-406
  • Peer Reviewed
• [Journal Article] Maturation of micro RNA is hormonally regulated by anuclear receptor (2009)
  • Author(s): Yamagata, K., et al.
  • Journal Title: Mol.Cell 36 Pages: 340-347
  • Peer Reviewed
• [Presentation] Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase(MMP)-13 expression (2011)
  • Author(s): K. Yamagata, S. Ikegaki, X. Li, Y. Minami
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-16
• [Presentation] Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP)-13 expression (2011)
  • Author(s): Kaoru Yamagata, Shunkichi Ikegaki, Xin Li, Yasuhiro Minami
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-16
• [Presentation] Rorファミリー受容体型チロシンキナーゼは大脳皮質神経幹細胞の維持に働く (2011)
  • Author(s): 遠藤光晴、土井亮助、西田満、南康博
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-12-13
• [Presentation] Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex (2011)
  • Author(s): 遠藤光晴、西田満、南康博
  • Organizer: 第63回日本細胞生物学会大会(ワークショップ)
  • Place of Presentation: 北海道大学クラーク会館
  • Year and Date: 2011-06-28
• [Presentation] Ror-family receptor tyrosine kinases regulate maintenance of neural progenitor cells in the developing neocortex (2011)
  • Author(s): 遠藤光晴、西田満、南康博
  • Organizer: 第63回日本細胞生物学会大会ワークショップ
  • Place of Presentation: 北海道大学クラーク会館
  • Year and Date: 2011-06-28
• [Presentation] Wnt5a-Ror2シグナルによる細胞極性・移動制御とがんの浸潤 (2010)
  • Author(s): 南康博、山形薫、西田満
  • Organizer: 第62回日本細胞生物学会大会(ミニシンポジウム)
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-05-20
• [Presentation] Wnt5a-Ror2シグナルによる細胞極性・移動制御とがんの浸潤 (2010)
  • Author(s): 南康博、山形薫、西田満
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-05-20
• [Presentation] Expression and functional analysis of Ror-family RTKs during developmental neurogenesis (2009)
  • Author(s): 遠藤光晴、任大勇、田中浩之、南康博
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-12-11
• [Presentation] Non-canonical Wnt signaling and its relationship with human diseases (2009)
  • Author(s): 南康博
  • Organizer: International Symposium Analyses of Developmental Phenomena
  • Place of Presentation: 島根大学 (島根県)
  • Year and Date: 2009-10-30
• [Presentation] Wnt5a・Ror2受容体型チロシンキナーゼによる細胞極性・移動制御におけるタンパク質リン酸化の役割 (2009)
  • Author(s): 南康博、西田満
  • Organizer: 第82回日本生化学大会(シンポジウム)
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2009-10-21
• [Presentation] Wnt5a・Ror2受容体型チロシンキナーゼによる細胞極性・移動制御におけるタンパク質リン酸化の役割 (2009)
  • Author(s): 南康博, 西田満
  • Organizer: 日本生化学会大会
  • Place of Presentation: 神戸国際会議場 (兵庫県)
  • Year and Date: 2009-10-21
• [Presentation] Non-canonical Wnt signaling and human diseases (2009)
  • Author(s): 南康博
  • Organizer: 6 the Meeting of Bone Biology Forum
  • Place of Presentation: 富士教育研修所 (静岡県)
• [Book] The Receptor Tyrosine Kinase Handbook (2012)
  • Author(s): Endo, M., Nishita, M., Doi, R., Minami, Y.
  • Publisher: Springer Science(in press)
• [Book] 非古典的Wntシグナルによる極性と幹細胞性維持の制御:生体の科学 (2012)
  • Author(s): 遠藤光晴、南康博
• [Book] The Receptor Tyrosine Kinase Handbook (chapter : Ror receptor family) (2012)
  • Author(s): Endo. M., Nishita, M., Doi, R., Minami, Y.
  • Publisher: Springer Science(印刷中)
• [Book] Wnt5aとRor2によるシグナル伝達と細胞機能制御:医学のあゆみ(生体システムとしてのWntシグナル・ネットワーク研究) (2010)
  • Author(s): 西田満、モハメド・アンワル・ハック、南康博
• [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/
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/medzoo/
• [Patent(Industrial Property Rights)] 疾患モデルとしての細胞種・組織特異的Ror2ノックアウトマウス (2011)
  • Inventor(s): 南康博、西田満、可児修一
  • Industrial Property Rights Holder: 神戸大学
  • Industrial Property Number: 2011-071014
  • Filing Date: 2011-03-28