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2004 Fiscal Year Final Research Report Summary

Molecular dissection of the physiological role of bioactive sphingosine-1-phosphate and Edg receptors

Research Project

Project/Area Number 15390063
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General physiology
Research InstitutionKanazawa University

Principal Investigator

TAKUWA Yho  Kanazawa University, Graduate School of Medical Science, Professor, 医学系研究科, 教授 (60171592)

Co-Investigator(Kenkyū-buntansha) SUGIMOTO Naotoshi  Kanazawa University, Graduate School of Medical Science, Assistant Professor, 医学系研究科, 講師 (80272954)
TAKUWA Noriko  Kanazawa University, Graduate School of Medical Science, Research Associate, 医学系研究科, 助手 (70150290)
YOSHIOKA Kazuaki  Kanazawa University, Graduate School of Medical Science, Research Associate, 医学系研究科, 助手 (80333368)
Project Period (FY) 2003 – 2004
Keywordssphingosine-1-phosphate / Edg / cell motility / Rac / Rho
Research Abstract

In order to delineate physiological and pathophysiological roles of sphingosine-1-phosphate (S1P), we conducted the following in vitro and in vivo investigations. S1P and its receptors regulate cell motility both positively and negatively. The S1P receptors Edg1 and Edg3 mediate Rac stimulation and thereby chemotaxis via Gi, whereas Edg5 mediates Rac inhibition and cell migration inhibition via G12/13 and Rho. Available evidence suggests that S1P could affect vascular smooth muscle accumulation in injured blood vessels. We found that S1P stimulated mRNA expression of platelet-derived growth factor (PDGF) A and B chains in neointimal smooth muscle. This stimulatory effect was mediated via Edg1-Gi-Ras-ERK/p38MAPK and Edg3/Edg5-Rho-Rho kinase. The ERK and p38MAPK mediated stimulation of KLF5 expression, which was necessary and sufficient for PDGF gene expression. S1P inhibits migration of vascular smooth muscle cells. This action was accompanied by Rac inhibition. Interestingly, both G12/13 and Gq were involved in S1P-induced Rac inhibition in vascular smooth muscle cells. In addition to Edg1 and Edg3, vascular endothelial cells express Edg5, which mediates inhibition of endothelial cell migration and capillary like tube formation. We generated Edg1-transgenic and sphingosine kinase-transgenic mice, and analyzed their phenotypes. Preliminary results show that S1P-Edg system is involved in the homeostasis of the cardiovascular system.

  • Research Products

    (20 results)

All 2004 2003

All Journal Article (20 results)

  • [Journal Article] Blood lipid mediator sphingosine-1-phosphate potently stimulates platelet derived growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-dependent induction of kruppel-like factor 5.2004

    • Author(s)
      S.Usui
    • Journal Title

      J.Biol.Chem 279

      Pages: 12300-12311

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Overexpression of phospholopase D prevents actinomycin D induced apoptosis through potentiation of phosphoinositide 3-kinase signaling pathways in Chinese hamster ovary cells.2004

    • Author(s)
      M.Yamada
    • Journal Title

      Biochem.J. 378

      Pages: 649-656

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells.2004

    • Author(s)
      D.Shida, T.Watanabe, T.Sakai, R.Suzuki, H.Ohta, Y.Takuwa, H.Nagawa
    • Journal Title

      Exp Cell Res. 301

      Pages: 168-178

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Blood lipid mediator sphingosine-1-phosphate potently stimulates platelet derived growth factor-A and -B chain expression through S1P1-Gi-Ras-MAPK-dependent induction of kruppel-like factor 5.2004

    • Author(s)
      S.Usui, N.Sugimoto, N.Takuwa, S.Sakagami, S.Takata, S.Kaneko, Y.Takuwa.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 12300-12311

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Overexpression of phospholopase D prevents actinomycin D induced apoptosis through potentiation of phosphoinositide 3-kinase signaling pathways in Chinese hamster ovary cells.2004

    • Author(s)
      M.Yamada, Y.Banno, Y.Takuwa, M.Koda, A.Hara, Y.Nozawa.
    • Journal Title

      Biochem.J. 378

      Pages: 649-656

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dual mode regulation of migration by lysophosphatidic acid in human gastric cancer cells.2004

    • Author(s)
      D.Shida, J.Kitayama, H.Yamaguchi, K.Hama, J.Aoki, H.Arai, H.Yamashita, K.Mori, A.Sako, T.Konishi, T.Watanabe, T.Sakai, R.Suzuki, H.Ohta, Y.Takuwa, H.Nagawa.
    • Journal Title

      Exp Cell Res. 301(2)

      Pages: 168-178

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of phospholipase D in insulin-like growth factor-I-induced activation of extracellular signal-regulated kinase, but not phosphatidylinositol 3-kinase or Akt, in chinese hamster ovary cells.2003

    • Author(s)
      Y.Banno
    • Journal Title

      Biochem.J. 369

      Pages: 363-368

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Antiproliferative action of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5.2003

    • Author(s)
      H.Ikeda
    • Journal Title

      Gastroenterology. 124

      Pages: 459-469

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibitory and stimulatory regulation of Rac and cell motility by the G12/13-Rho-and the Gi-pathways integrated downstream of a single G protein coupled sphingosine-1-phosphate receptor isoform.2003

    • Author(s)
      N.Sugimoto
    • Journal Title

      Mol.Cell. 23

      Pages: 1534-1545

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lysophosphatidic acid enhances metastatic potential of human colon carcinoma DLD1 cells through LPA1.2003

    • Author(s)
      D.Shida
    • Journal Title

      Cancer Res. 63

      Pages: 1706-1711

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils.2003

    • Author(s)
      J.Xu
    • Journal Title

      Cell 278

      Pages: 201-214

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ligand-dependent inhibition of B16 melanoma cell migration and invasion via endogenous S1P2 G protein-coupled receptor requirement of inhibition of cellular Rac activity.2003

    • Author(s)
      K.Arikawa
    • Journal Title

      J.Biol.Chem. 278

      Pages: 32841-32851

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and hematogenous metastasis of melanoma cells.2003

    • Author(s)
      H.Yamaguchi
    • Journal Title

      Biochem.J. 374

      Pages: 715-722

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Involvement of phospholipase D in insulin-like growth factor-I-induced activation of extracellular signal-regulated kinase, but not phosphatidylinositol 3-kinase or Akt, in chinese hamster ovary cells.2003

    • Author(s)
      Y, Banno, Y.Takuwa, M.Yamada, N.Takuwa, K.Ohguchi, A.Hara, Y.Nozawa.
    • Journal Title

      Biochem.J. 369

      Pages: 363-368

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Antiproliferative action of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5.2003

    • Author(s)
      H.Ikeda, H.Satoh, M.Yanase, Y.Inoue, T.Tomiya, M.Arai, K.Tejima, K.Nagashima, H.Maekawa, N.Yahagi, Y.Tamtomi, S.Sakurada, Y.Takuwa, I.Ogara, S.Kimura, K.Fujiwara.
    • Journal Title

      Gastroenterology. 124

      Pages: 459-469

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibitory and stimulatory regulation of Rac and cell motility by the G_<12/13>-Rho-and the G_i-pathways integrated downstream of a single G protein coupled sphingosine-1-phosphate receptor isoform.2003

    • Author(s)
      N.Sugimoto, N.Takuwa, H.Okamoto, S.Sakurada, Y.Takuwa.
    • Journal Title

      Mol.Cell.Biol. 23

      Pages: 1534-1545

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Lysophosphatidic acid enhances metastatic potential of human colon carcinoma DLD1 cells through LPA1.2003

    • Author(s)
      D.Shida, J.Kitayama, H.Yamaguchi, Y Okaji, NH.Tsuno, T.Watanabe, Y Takuwa, H.Nagawa.
    • Journal Title

      Cancer Res. 63

      Pages: 1706-1711

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Divergent signals and cytoskeletal Assemblies regulate self-organizing polarity in neutrophils.2003

    • Author(s)
      J.Xu, F.Wang, A.V.Keymeulen, P.Herzmark, A.Straight, K.Kelly, Y.Takuwa, N.Sugimoto, T.Mitchison, H.R.Bourne.
    • Journal Title

      Cell 114

      Pages: 201-214

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ligand-dependent inhibition of B16 melanoma cell migration and invasion via endogenous S1P2 G protein-coupled receptor requirement of inhibition of cellular Rac activity.2003

    • Author(s)
      K.Arikawa, N.Takuwa, H.Yamaguchi, N.Sugimoto, J.Kitayama, H.Nagawa, K.Takehara, Y.Takuwa.
    • Journal Title

      J.Biol.Chem. 278

      Pages: 32841-32851

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sphingosine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and hematogenous metastasis of melanoma cells.2003

    • Author(s)
      H.Yamaguchi, J.Kitayama, N.Takuwa, K.Arikawa, I.Inoki, K.Takehara, H.Nagawa, Y.Takuwa.
    • Journal Title

      Biochem.J. 374

      Pages: 715-722

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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