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Signal transduction to nucleus by phosphatidylinositol 3-kinase

Research Project

Project/Area Number 12460039
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionThe University of Tokyo

Principal Investigator

FUKUI Yasuhisa  Grad. Sch. Agriculture and Life Science, The University of Tokyo, Professor, 大学院・農学生命科学研究科, 教授 (00181248)

Co-Investigator(Kenkyū-buntansha) IHARA Sayoko  Grad. Sch. Agriculture and Life Science, The University of Tokyo, Assistant, 大学院・農学生命科学研究科, 助手 (80292788)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2001: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2000: ¥9,100,000 (Direct Cost: ¥9,100,000)
Keywordsphosphoinositides / PH domain / GEF / PIP_3 / Rac / Ruffling / signal transduction / growth factors / ホスファチジルイノシトール3キナーゼ / 核移行 / グアニンヌクレオチド交換因子 / GTPase促進活性因子 / ラッフル膜 / Gタンパク質 / 核外輸送
Research Abstract

We have explored the roles of PIP_3 binding proteins, especially on Swap-70 protein, in order to understand the signal transduction of phosphatidylinositol 3-kinase (PI3K).
Swap-70 has been identified as a ubiquitous distribution suggested its other functions. Our study revealed that Swap-70 moved to the membrane ruffles after stimulation with growth factors and that this protein was a guanine nucleotide exchange factor (GEE) for Rac. This GEF activity was refused for signaling from growth factor receptors to Rac via PI3K. Kidney cell cultures established from Swap-70 deficient mice showed impaired membrane ruffling after EGF stimulation compared with those for wild type mice.
Swap-70 contains a DH domain, which exhibits the GEF activity, and a PH domain responsible for PIP3 binding. The PH domain binds to the DH domain to inhibit the GEF activity. This binding was abolished to PIP_3, suggestion that PIP_3 releases the DH domain from the inhibitory effect of the PH domain.

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kobayashi, S., et al.: "Membrane recruitment of DOCK18O by binding to PtdIns(3,4,5)P3"Biochem J.. 354. 73-78 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Higuchi, M. et al.: "Akt mediates Rac/Cdc42-regulated cell motility in growth factor-stimulated cells and knockout cells"Curr Biol. 11. 1958-1962 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Harada, Y., et al.: "Novel role of phosphatidylinositol 3-kinase in CD28-mediated costimulation"J. Biol. Chem.. 276. 9003-9008 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinohara.M., et al.: "SWAP-70 is a guanine nucleotide exchange factor that mediates signaling of membrane ruffling"Nature. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi, S., et al.: "Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3"Biochem J.. 354. 73-78 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Higuchi, M., et al.: "Akt mediates Rac/Cdc42-regulated cell motility in growth factor-stimulated cells and in invasive PTEN knockout cells"Curr Biol. 11. 1958-1962 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Harada, Y., et al.: "Novel role of phosphatidylinositol 3-kinase in CD28-mediated costimulation"J. Biol. Chem.. 276. 9003-9008 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinohara, M., et al.: "SWAP-70 is a guanine nucleotide exchange factor that mediates signaling of membrane ruffling"Nature. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi, S., et al.: "Membrane recruitment of DOCK180 by binding to PtdIns(3, 4, 5)P3"Biochem J.. 354. 73-78 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Higuchi, M., et al.: "Akt mediates Rac/Cdc42-regulated cell motility in growth factor-stimulated cells and knockout cells"Curr Biol. 11. 1958-1962 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Harada, Y., et al.: "Novel role of phosphatidylinositol 3-kinase in CD28-mediated costimulation"J. Biol. Chem.. 276. 9003-9008 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinohara, M., et al.: "SWAP-70 is a guanine nucleotide exchange factor that mediates signaling of membrane ruffling"Nature. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Morisaki,N., et al.: "Phosphorylation of unnatural phosphatidylinositols with phosphatidylinositol 3-kinase."Tetrahedron. 56. 2603-2614 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishio,Y., et al.: "Quantification of phosphatidylinositol 3,4,5-trisphosphate by liposome lysis assay with specific monoclonal antibodies."Anal.Biochem.. 285. 270-273 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yokogawa,T., et al.: "Evidence that 3'-phosphorylated Polyphosphoinositides are generated at the nuclear surface use of immunostaining technique with monoclonal antibodies specific for PI 3,4-P_2."FEBS Letters. 473. 222-226 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Harada Y., et al: "Novel role of PI3-K in CD28-mediated costimulation."J.Biol.Chem.. (in press). (2000)

    • Related Report
      2000 Annual Research Report

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

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