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

Crosstalk between STATs and small GTPases in the control of cell division and differentiation.

Research Project

Project/Area Number 16209032
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

KITAMURA Toshio  The University of Tokyo, The Institute of Medical Science, Professor, 医科学研究所, 教授 (20282527)

Co-Investigator(Kenkyū-buntansha) NOSAKA Tetsuya  Mie University Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (30218309)
NAKAJIMA Hideaki  The University of Tokyo, The Institute of Medical Science, Project Associate Professor, 医科学研究所, 特任助教授 (30217723)
KAWASHIMA Toshiyuki  The University of Tokyo, The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (10306839)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥48,490,000 (Direct Cost: ¥37,300,000、Indirect Cost: ¥11,190,000)
Fiscal Year 2006: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2005: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2004: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000)
Keywordsnuclear transport assay / STAT3 / STAT5 / importin / Rac1 / Cytokinesis / GAP / PhoA / インポーチン / Rac1 / 細胞質分裂 / GAP / RhoA / STAT / 低分子量G蛋白質 / 転写 / GAP蛋白質
Research Abstract

In this research project, we have investigated cross-talk between activation of STAT3/STAT5 and Rho family small GTPases. In 2004-2005, using mouse embryonic fibroblasts where Racl can be conditionally deleted by Cre recombinase as well as a dominant negative Racl and siRNA for Racl, we demonstrated that Racl is essential for nuclear transport of STAT3 and STAT5. However, the underlying molecular mechanisms remained elusive. In 2006, we investigated how Racl controls nuclear transport of STAT3 and STAT5. To this end, we established a nuclear transport assay using permialized cells and recombinant proteins produced in F9 insect cells. The nuclear transport assay revealed that an active form of Racl, MgcRacGAP and importin a/b are required for the nuclear transport of phosphorylated STAT3 and STAT5. Interestingly, STAT/Racl/MgcRacGAP complex binds importin a only when Racl is in its GTP-bound form, indicating that MgcRacGAP plays an important role in the binding and dissociation of STAT and importins (Kawashima et al., J Cell Biol, 2006). We also found that MgcRacGAP harbors nuclear localization signal (NLS). Although STAT3 and 5 do not possess typical NLS, the present results show that MgcRacGAP and Racl works as a nuclear shaperon for the activated STAT3 and 5. In addition, we also found that MgcRacGAP also binds JAK2 that is known to phosphorylate STAT proteins. Knockdown of either MgcRacGAP or Racl not only inhibited nuclear transport of STAT3/5 but also attenuated their phosphorylation. Altogether, the present results suggested that MgcRacGAP and Racl plays critical roles in the nuclear transport of STAT3 and STAT5 as well as transport to the plasma membrane and activation of these transcription factors.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (41 results)

All 2006 2005 2004 Other

All Journal Article (41 results)

  • [Journal Article] Integrin allbb3 induces the adhesion and activation of mast cells through interaction with fibrinogen.2006

    • Author(s)
      Oki, T et al.
    • Journal Title

      J. Immunol. 176

      Pages: 52-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3.2006

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

      Int. J. Hematol. 84

      Pages: 54-59

    • NAID

      10020357815

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPa.2006

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

      EMBO J. 25

      Pages: 3398-3410

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Racl and a GTPase activating protein MgcRacGAP are required for nuclear translocation of STAT transcription factors.2006

    • Author(s)
      Kawashima. T et al.
    • Journal Title

      J. Cell Biol. 175

      Pages: 937-946

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Integrin aIIbb3 induces the adhesion and activation of mast cells through interaction with fibrinogen.2006

    • Author(s)
      Oki, T., et al.
    • Journal Title

      J. Immunol. 176

      Pages: 52-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3.2006

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

      Int. J. Hematol. 84

      Pages: 54-59

    • NAID

      10020357815

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPa.2006

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

      EMBO J. 25

      Pages: 3398-3410

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Rac1 and a GTPase activating protein MgcRacGAP are required for nuclear translocation of STAT transcription factors.2006

    • Author(s)
      Kawashima, T., et al.
    • Journal Title

      J. Cell Biol. 175

      Pages: 937-946

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Integrin αIIbβ3 induces the adhesion and activation of mast cells through interaction with fibrinogen.2006

    • Author(s)
      沖 俊彦
    • Journal Title

      J. Immunol. 176

      Pages: 52-60

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells.2006

    • Author(s)
      中島 秀明
    • Journal Title

      Biochem. Biophys. Res. Commun. 340

      Pages: 35-42

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Tyk2 is dispensable for induction of myeloproliferative disease by mutant FLT3.2006

    • Author(s)
      中島 秀明
    • Journal Title

      Int. J. Hematol. 84

      Pages: 54-59

    • NAID

      10020357815

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPα.2006

    • Author(s)
      福地 由美
    • Journal Title

      EMBO J. 25

      Pages: 3398-3410

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Racl and a GTPase activating protein MgcRacGAp are required for nuclear translocation of STAT transcription factors.2006

    • Author(s)
      川島 敏行
    • Journal Title

      J. Cell Biol. 175

      Pages: 937-946

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Integrin αIIbβ3 induces the adhesion and activation of mast cells through interaction with fibrinogen2006

    • Author(s)
      沖俊彦
    • Journal Title

      J.Immunol. 176

      Pages: 52-60

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells2006

    • Author(s)
      中島秀明
    • Journal Title

      Biochem.Biophys.Res.Commun. 印刷中

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple lineage leukemogenesis.2005

    • Author(s)
      Ono, R et al.
    • Journal Title

      J. Clin. Invest. 115

      Pages: 919-929

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ect-2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.2005

    • Author(s)
      Oceguera-Yanez, F et al.
    • Journal Title

      J. Cell Biol. 168

      Pages: 221-232

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia.2005

    • Author(s)
      Urano, A, et al.
    • Journal Title

      Mol. Cell. Biol. 15

      Pages: 6834-6845

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective activation of STAT5 unveils its role in stem cell self-renewal of normal and leukemic hematopoiesis.2005

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

      J. Exp. Med. 202

      Pages: 169-179

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human leukemias with mutated FLT3 kinase are sinergistically sensitive to FLT3 and Hsp90 inhibitors : the key role of the STAT5 signal transduction pathway.2005

    • Author(s)
      Yao, R, et al.
    • Journal Title

      Leukemia 19

      Pages: 1605-1612

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The constitutive centromere component CENP-50 is required for recovery from spindle damage.2005

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

      Mol. Cell. Biol. 25

      Pages: 10315-10328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Disruption of Sept6, a fusion partner gene of Mixed Lineage Leukemia (MLL), does not affect the ontogeny, leukemogenesis induced by MLL-SEPT6, or the phenotype induced by the loss of Sept4.2005

    • Author(s)
      Ono, R et al.
    • Journal Title

      Mol. Cell. Biol. 25

      Pages: 10965-10978

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pen-2 is incorporated into the g-secretase complex through binding to transmembrane domain 4 of presenilin 1.2005

    • Author(s)
      Watanabe, N et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 41967-41975

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple lineage leukemogenesis.2005

    • Author(s)
      Ono, R., et al.
    • Journal Title

      J. Clin. Invest. 115

      Pages: 919-929

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ect-2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.2005

    • Author(s)
      Oceguera-Yanez, F., et al.
    • Journal Title

      J. Cell Biol. 168

      Pages: 221-232

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia.2005

    • Author(s)
      Urano, A., et al.
    • Journal Title

      Mol. Cell. Biol. 15

      Pages: 6834-6845

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective activation of STAT5 unveils its role in stem cell self-renewal of normal and leukemic hematopoiesis.2005

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

      J. Exp. Med. 202

      Pages: 169-179

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human leukemias with mutated FLT3 kinase are sinergistically sensitive to FLT3 and Hsp90 inhibitors : the key role of the STAT5 signal transduction pathway.2005

    • Author(s)
      Yao, R., et al.
    • Journal Title

      Leukemia 19

      Pages: 1605-1612

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The constitutive centromere component CENP-50 is required for recovery from spindle damage.2005

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

      Mol. Cell. Biol. 25

      Pages: 10315-10328

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Disruption of Sept6, a fusion partner gene of Mixed Lineage Leukemia (MLL), does not affect the ontogeny, leukemogenesis induced by MLL-SEPT6, or, the phenotype induced by the loss of Sept4.2005

    • Author(s)
      Ono, R., et al.
    • Journal Title

      Mol. Cell. Biol. 25

      Pages: 10965-10978

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pen-2 is incorporated into the g-secretase complex through binding to transmembrane domain 4 of presenilin 1.2005

    • Author(s)
      Watanabe, N., et al.
    • Journal Title

      J. Biol. Chem. 280

      Pages: 41967-41975

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Dimerization of MLL fusion proteins and FLT3 activation synergize to induce multiple lineage leukemogenesis2005

    • Author(s)
      小埜良一
    • Journal Title

      J.Clin.Invest. 115

      Pages: 919-929

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia2005

    • Author(s)
      浦野敦司
    • Journal Title

      Mol.Cell.Biol. 15

      Pages: 6834-6845

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The constitutive centromere component CENP-50 is required for recovery from spindle damage2005

    • Author(s)
      箕嶋幸範
    • Journal Title

      Mol.Cell.Biol. 25

      Pages: 10315-10328

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Disruption of Sept6, a fusion partner gene of Mixed Lineage Leukemia (MLL), does not affect the ontogeny, Leukemogenesis induced by MLL-SEPT6, or the phenotype induced by the loss of Sept42005

    • Author(s)
      小埜良一
    • Journal Title

      Mol.Cell.Biol. 280

      Pages: 10965-10978

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Two-step model of leukemogenesis in multiple lineages by dimerization of MLL fusion protein.2005

    • Author(s)
      Ono, R.
    • Journal Title

      J.Clin.Invest. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Infertility with defective spermiogenesis in mice lacking AF5q31, the target of chromosomal translocation in human infant leukemia.2005

    • Author(s)
      Urano, A.
    • Journal Title

      Mol.Cell.Biol. (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Vasorin, a novel TGF-β binding protein expressed in vascular smooth muscle cells, modulates the arterial response to injury in vivo.2004

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

      Pro.Natl.Acad.Sci.USA. 101

      Pages: 10732-10737

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A GTPase activating protein binds STAT3 and is required for IL-6-induced STAT3 activation and differentiation of a leukemic cell line.2004

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

      Blood 104

      Pages: 3550-3557

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human placenta-derived cells have mesenchymal stem/progenitor cell potential.2004

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

      Stem Cell 22

      Pages: 649-658

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Functional analysis of an activating receptor LMIR4 as a counterpart of an inhibitory receptor LMIR3.

    • Author(s)
      伊沢 久未
    • Journal Title

      J. Biol. Chem. (in press.)

    • Related Report
      2006 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi