• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Regulation and function of cytoskeleton reorganization by signaling molecules in hematopoietic cells.

Research Project

Project/Area Number 17590437
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

TANAKA Yoshihiko  Kyushu University, Medical Institute of Bioregulation, Research Associate, 生体防御医学研究所, 助手 (00398083)

Co-Investigator(Kenkyū-buntansha) FUKUI Yoshinori  Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (60243961)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
KeywordsSignal transduction / Immunology / Cell, tissue / Development, differentiation / Biotechnology / DOCK2 / SLAT / Vav / 細胞骨格 / サイトカイン
Research Abstract

Cytoskeleton reorganization regulates cell polarity, migration and signal transduction in various cells, but the precise role in hematopoietic cells is still unclear. In this study, we focused on several aspects of the regulation and function of cytoskeleton reorganization molecules, such as DOCK2,Vavl, and SLAT, in hematopoietic cell activation. We found that DOCK2 deficiency causes marked reduction of Val4 NKT cells in the thymus, liver, and spleen. Studies using bone marrow chimeras indicated that development of Val4 NKT cell requires DOCK2 expression in T cell precursors, but not in APCs. We also reported that DOCK2 regulates motility and polarity during neutrophil chemotaxis. In DOCK2-deficient neutrophils, chemoattractant-induced activation of both Rac1 and Rac2 were severely impaired, resulting in the loss of polarized accumulation of F-actin and phosphatidylinositol 3,4,5-triphosphate (PIP_3) at the leading edge. These results indicate that during neutrophil chemotaxis DOCK2 regulates leading edge formation through PIP_3-dependent membrane translocation and Rac activation. In addition, we showed that Vavl is selectively required for IL-4 and c-Maf expression, a requirement reflecting, at least in part, the dependence of c-Maf expression of Ca^<2+>/NFAT signaling. Finally, we found that SLAT regulates Th1 and Th2 lung inflammatory responses by controlling Ca^<2+>/NFAT signaling. Thus, we demonstrated several critical aspects for cytoskeleton reorganization in hematopoietic cells using a combination of biochemical and genetic approaches. Future work should be aimed at defining the precise mechanisms through which these molecules regulate the function of cytoskeleton reorganization.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (33 results)

All 2007 2006 2005

All Journal Article (33 results)

  • [Journal Article] SLAT regulates Thl and Th2 lung inflammatory responses by controlling Ca^<2+>/NFAT signaling.2007

    • Author(s)
      Becart, S. et al.
    • Journal Title

      J. Clin. Invest. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-l-phosphate-mediatsd egress.2007

    • Author(s)
      Nombela-Arrieta C. et al.
    • Journal Title

      J. Exp. Med. 204

      Pages: 497-510

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Shignella IpgBl promotes bacterial entry through the ELMO-Dock180 machinery.2007

    • Author(s)
      Handa, Y. et al.
    • Journal Title

      Nat. Cell Biol. 9

      Pages: 121-128

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] SLAT regulates Th1 and Th2 lung inflammatory responses by controlling Ca^<2+>/NFAT signaling.2007

    • Author(s)
      Becart.S., et al.
    • Journal Title

      J.Clin.Invest. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediatsd egress.2007

    • Author(s)
      Nombela-Arrieta C., et al.
    • Journal Title

      J.Exp.Med. 204

      Pages: 497-510

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Shignella IpgBl promotes bacterial entry through the ELMO-Dock 180 machinery.2007

    • Author(s)
      Handa, Y., et al.
    • Journal Title

      Nat.Cell Biol. 9

      Pages: 121-128

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A central role for DOCK2during interstitial lymphocyte motility and sphingosine-1-phosphate-mediatsd egress.2007

    • Author(s)
      Nombela-Arrieta C. et al.
    • Journal Title

      J.Exp.Med. 204

      Pages: 497-510

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Shignella IpgBl promotes bacterial entry thorough the ELMO-Dock180 machinery.2007

    • Author(s)
      Handa, Y. et al.
    • Journal Title

      Nat.Cell Biol. 9

      Pages: 121-128

    • Related Report
      2006 Annual Research Report
  • [Journal Article] DOCK2 is required in T cell precursors for development of Vα14 natural killar T (NKT) cells.2006

    • Author(s)
      Kunisaki, Y. et al.
    • Journal Title

      J. Immunol. 174

      Pages: 4640-4645

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis.2006

    • Author(s)
      Kunisaki, Y. et al.
    • Journal Title

      J. Cell Biol. 174

      Pages: 647-652

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Impaired activation and localization of LAT in anergic T cells as a consequence of a selective palmitoylation defect.2006

    • Author(s)
      Hundt, M. et al.
    • Journal Title

      Immunity 24

      Pages: 513-522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin α4β1.2006

    • Author(s)
      Garcia-Bernal, D. et al.
    • Journal Title

      J.Immunol. 177

      Pages: 5215-5225

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration.2006

    • Author(s)
      Shulman, Z. et al.
    • Journal Title

      Blood 108

      Pages: 2150-2158

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 好中球遊走を制御するRac活性化分子DOCK22006

    • Author(s)
      福井宣規
    • Journal Title

      実験医学 24

      Pages: 3269-3276

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] DOCK2 is required in T cell precursors for development of Vα14 natural killar T (NKT) cells.2006

    • Author(s)
      Kunisaki, Y., et al.
    • Journal Title

      J.Immunol. 176

      Pages: 4640-4645

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis.2006

    • Author(s)
      Kunisaki, Y., et al.
    • Journal Title

      J.Cell Biol. 174

      Pages: 647-652

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Impaired activation and localization of LAT in anergic T cells as a consequence of a selective palmitoylation defect.2006

    • Author(s)
      Hundt, M., et al.
    • Journal Title

      Immunity 24

      Pages: 513-522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin α4β1.2006

    • Author(s)
      Garcia-Bernal, D., et al.
    • Journal Title

      J.Immunol. 177

      Pages: 5215-5225

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration.2006

    • Author(s)
      Shulman, Z., et al.
    • Journal Title

      Blood 108

      Pages: 2150-2158

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 is a Rac activator critical for neutrophil chemotaxis.2006

    • Author(s)
      Fukui, Y.
    • Journal Title

      Jikken igaku 24

      Pages: 3269-3276

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 is required in T cell precursors for development of Val4natural killar T(NKT) cells.2006

    • Author(s)
      Kunisaki, Y. et al.
    • Journal Title

      J.Immunol. 176

      Pages: 4640-4645

    • Related Report
      2006 Annual Research Report
  • [Journal Article] DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis.2006

    • Author(s)
      Kunisaki, Y. et al.
    • Journal Title

      J.Cell Biol. 174

      Pages: 647-652

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Impaired activation and localizarion of LAT in anergic T cells as a consequence of a selective palmitoylation degect.2006

    • Author(s)
      Hundt, M, et al.
    • Journal Title

      Immunity 24

      Pages: 513-522

    • Related Report
      2006 Annual Research Report
  • [Journal Article] DOCK2 is required for chemokine-promoted human T lymhocyte adhesion under shear stress mediated by the integnin α4β1.2006

    • Author(s)
      Garcia-Betnal, D. et al.
    • Journal Title

      J.Immunol. 177

      Pages: 5215-5225

    • Related Report
      2006 Annual Research Report
  • [Journal Article] DOCK2 is required in T cell precursors for development of Vα14 natural killar T (NKT) cells.2006

    • Author(s)
      Kunisaki, Y. et al.
    • Journal Title

      J.Immunol. (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Impaired activation and localization of LAT in anergic T cells as a consequence of a selective palmitoylation defect.2006

    • Author(s)
      Hundt, M. et al.
    • Journal Title

      Immunity (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Impaired IL-4 and c-Maf expression and enhanced Thl cell development in Vavl-deficient mice.2005

    • Author(s)
      Tanaka, Y. et al.
    • Journal Title

      Blood 106

      Pages: 1286-1295

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Deletion of DOCK2, a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection.2005

    • Author(s)
      Jiang, H. et al.
    • Journal Title

      J. Exp. Med. 202

      Pages: 1121-1130

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] リンパ球の運動性を制御する分子DOCK22005

    • Author(s)
      福井宣規
    • Journal Title

      医学のあゆみ 213

      Pages: 2915-2920

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Impaired IL-4 and c-Maf expression and enhanced Th1 cell development in Vavl-deficient mice.2005

    • Author(s)
      Tanaka, Y., et al.
    • Journal Title

      Blood 106

      Pages: 1286-1295

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Deletion of DOCK2,a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection.2005

    • Author(s)
      Jiang, H., et al.
    • Journal Title

      J.Exp.Med. 202

      Pages: 1121-1130

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] DOCK2 is a molecule that determines lymphocyte motility.2005

    • Author(s)
      Fukui Y.
    • Journal Title

      Igaku no ayumi 213

      Pages: 2915-2920

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Impaired IL-4 and c-Maf expression and enhanced Th1 cell development in Vav 1-deficient mice.2005

    • Author(s)
      Tanaka, Y. et al.
    • Journal Title

      Blood 106

      Pages: 1286-1295

    • Related Report
      2005 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi