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Biological analysis of signal transduction of Rho-Rho kinase

Research Project

Project/Area Number 12680648
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionOsaka Medical Center for Cancer and Cardiovascular Diseases

Principal Investigator

ITOH Kazuyuki  Osaka Medical Center for Cancer and Cardiovascular Diseases. Biology. Department Head, 研究所, 部長 (20301806)

Co-Investigator(Kenkyū-buntansha) YOSHIOKA Kiyoko  Osaka Medical Center for Cancer and Cardiovascular Diseases, Biology, Chief Investigator, 研究所, 主任研究員 (40342993)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsRho / Rho kinase (ROCK) / BMP / Bone formation / chemokine / lymphocyte / lysosome / intracellular trafficking / コラーゲン / stromal cell / Rho kinase(ROCK)
Research Abstract

During the course of this project, we elucidated the three novel function of molecular switch Rho-ROCK signaling. Firstly, collaborating with orthopedic professor Dr. Yoshikawa, Osaka University medical school, we found that the inhibitor for ROCK accelerate the bone formation induced by bone morphogenetic protein (BMP) without affecting the bone metabolism in animal. Employing several undifferentiated mesenchymal cell lines, it revealed that Rho-ROCK signaling negatively regulated the expression of BMP, thus the ROCK inhibitor released such inhibition leading to the enhancement of osteoblastic differentiation (3). We further analyzed the signaling of osteoblastic differentiation and found that MEK-MAPK signaling also negatively regulated the osteoblastic signaling, and that the specific inhibitor for MEK1 (PD98059) enhanced bone formation both in vitro and in vivo (6). Future study for clinical application for these results is currently undertaken. Secondary, collaborating with Spanis … More h professor Dr. Sanchez Madrid, we analyzed the signaling for chemokine (SDF-1α)-induced lymphocyte chemotaxis and found that Rho-ROCK-myosin (molecular motor) signaling plays a pivotal role for that migration similar to that of cancer invasion, which we have already reported previously. We also found that Rho-ROCK signaling involved microtubule dynamics in lymphocytes using same system (5). Since lymphocyte migration is critical for immune response, our results open a new field to control the immune response via the modulation of migration of lymphocytes. Lastly, collaborating with Dr. Nishimura, Kyusyu University, we found that Rho-ROCK signaling control lysosomal vesicle trafficking via changing the microtubule dynamics (1, 7). The mechanism for intracellular trafficking is now hot field, since it regulated the number of cellular function and one of the best molecular targets for the clinical therapy. Our results shed light to the critical function of cytoskeletal change induced by Rho-ROCK on the vesicle trafficking and pharmacological manipulation of such system for the treatment of several diseases including devastating cancer. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Nishimura, Y., Itoh, K., Yoshioka, K., Uehata, M., Himeno, M.: "Small GTPase Rho/Rho associated kinase as a novel regulator of intracellular redistribution of lysosomes in invasive tumor cells"Cell and Tissue Research. 301. 345-351 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saeki, Y., Hazeki, K., Hazeki, O., Ui, M., Itoh, K., Matsumoto, M., Toyoshima, K., Akedo, H., Seya, Y.: "Participation of a MEK-independent pathway in MAP kinase activation and modulation of cell growth in mouse hepatoma cell lines"Int.J.Mol.Med. 6. 155-160 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K., Yoshioka, K., Nakase, T., Yoshikawa, H.: "Stimulation of Bone Formation by Rho-associated Kinase Inhibitor"J.Bone Miner.Res.. 16. 235 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K., Yoshioka, K., Takagi, Y., Uehata, M.: "An Essential Role for LIM-Kinase in Breast Cancer Cell Invasion and Bone Metastasis"J.Bone Miner.Metab.. 19. 33 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Manzanares, MV., Cabrero JR., Rey, M., Martinez, MP., Ursa, A., Itoh, K., Madrid, FS.: "A role for the Rho-p160Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-1α-induced lymphocyte actomyosin and microtubular organization and chemotaxis"J.Immunology. 168. 400-410 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Higuchi, C., Myoui, A., Hashimoto, N., Kuriyama, K., Yoshioka, K., Yoshikawa, H., Itoh, K.: "Continuous inhibition of MAPK signaling promotes the early osteoblastic differentiation and mineralization of extracellular matrix"J.Bone Miner.Res.. 17. 1785-1794 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishimura, Y., Itoh, K., Yoshioka, K., Ikeda, K., Himeno, M.: "A Role for Small GTPase RhoA in Regulating Intracellular Membrane Traffic of Lysosomes in Invasive Rat Hepatoma Cells"The Histochemical Journal. 34. 189-213 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishimura, Y., Itoh, K., Yoshioka, K., Uehata, M. and Hiraeno, M.: "Small GTPase Rho/Rho associated kinase as a novel regulator of intracellular redistribution of lysosomes in invasive tumor cells"Cell and Tissue Res.. 301. 341-351 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saeki, Y., Hazeki, K., Hazeki, O., Ui, M., Itoh, K., Matsumoto, M., Toyoshima, K., Akedo, H. and Seya, Y.: "Participation of a MEK-independent pathway in MAP kinase activation and modulation of cell growth in mouse hepatoma cell lines"Int. J. Mol. Med.. 6. 155-160 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K., Yoshioka, K., Nakase, T. and Yoshikawa H.: "Stimulation of Bone Formation by Rho-associated Kinase Inhibitor"J. Bone Miner. Res.. 16. S235 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K., Yoshioka, K, Takagi, Y. and Uehata, M.: "An Essential Role for LIM- Kinase in Breast Cancer Cell Invasion and Bone Metastasis"J. Bone Miner. Metab.. 19. 33 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Manzanares, MV., Cabrero JR., Rey, M., Martinez, MR., Ursa, A., Itoh. K. and Madrid, FS.: "A role for the Rho-p160Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-lα-induced lymphocyte actomyosin and microtubular organization and chemotaxis"J. Immunology. 168. 400-410 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Higuchi, C., Myoui, A., Hashimoto, N., Kuriyama, K., Yoshioka, K., Yoshikawa, H. and Itoh, K.: "Continuous inhibition of MAPK signaling promotes the early osteoblastic differentiation and mineralization of extracellular matrix"J. Bone Miner. Res.. 17. 1785-1794 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nishimura, Y., Itoh, K., Yoshioka, K., Ikeda, K., Himeno, M.: "A Role for Small GTPase RhoA in Regulating Intracellular Membrane Traffic of Lysosomes in Invasive Rat Hepatoma Cells"The Histochemical Journal. 34. 189-213 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh, K., Yoshioka, K., Nakase, T., Yoshikawa H.: "Stimulation of Bone Formation by Rho-associated Kinase Inhibitor"J.Bone Miner.Res.. 16. 235 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itoh, K., Yoshioka, K, Takagi, Y., Uehata, M.: "An Essential Role for LIM-Kinase in Breast Cancer Cell Invasion and Bone Metastasis"J.Bone Miner.Metab.. 19. 33 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Manzanares, MV., Cabrero JR., Rey, M., Martinez, MP., Ursa, A., Itoh, K., Madrid, FS.: "A role for the Rho-p160Rho coiled-coil kinase axis in the chemokine stromal cell-derived factor-1α-induced lymphocyte actomyosin and microtubular organization and chemotaxis"J.Immunology. 168. 400-410 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Naka, M., Araki, N., Nakanishi, H., Itoh, K., Mano, M., Ishiguro, S., Brujin, DR., Myoui, A., Ueda, T., Yoshikawa, K.: "Expression of SSX genes in human osteosarcomas"Int.J.Cancer. 98. 640-642 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nishimura,Y.,Itoh,K.,Yoshioka,K.,Uehata,M.and Himeno M: "Small GTPase Rho/Rho associated kinase as a novel regulator of intracellular redistribution of lysosomes in invasive tumor cells"Cell and Tissue Research. 301. 345-351 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saeki,Y.,Hazeki,K.,Hazeki,O.,Ui,M.,Itoh,K.,Matsumoto,M.,Toyoshima,K.,Akedo,H.& Seya,Y.: "Participation of a MEK-independent pathway in MAP kinase activation and modulation of cell growth in mouse hepatoma cell lines"Int.J.Mol.Med. 6. 155-160 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Itoh,K.and Yoshioka,K: "Key molecules that regulate breast cancer cells to invade new tissues"ASCB Press Book. 7 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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