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2006 Fiscal Year Final Research Report Summary

Analysis of subcellular region-specific activation of Ras and Rho family GTPases and its application

Research Project

Project/Area Number 17370050
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionKobe University

Principal Investigator

SATOH Takaya  Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20251655)

Co-Investigator(Kenkyū-buntansha) UEDA Shuji  Kobe University, Graduate School of Medicine, COE Researcher, 大学院・医学系研究科, COE研究員 (50379400)
Project Period (FY) 2005 – 2006
KeywordsRac1 / GLUT4 / skeletal muscle / insulin / endocytosis / Ost / Rap1 / M-ras
Research Abstract

1. Analysis of the role for Rac1 in insulin-dependent glucose uptake in skeletal muscle cells: By using the L6 myoblast cell line, translocation of GLUT4 to the plasma membrane upon ectopic expression of constitutively activated Rac1 and lowered GLUT4 translocation in response to insulin upon downregulation of the expression of endogenous Rac1 by siRNA were observed. These effects were tried to be evaluated in mice by adenovirus-mediated gene transfer and targeted gene disruption. 2. Analysis of the negative regulation of clathrin-dependent receptor endocytosis by Rac1: Ectopic expression of constitutively activated Rac1 potently inhibited transferrin receptor endocytosis. The guanine nucleotide exchange factor Ost-III, but not its splice variants Ost-I and Ost-II, also abolished transferrin receptor endocytosis, suggesting that Ost-III may act as a specific activator for Rac1 that is involved in the negative regulation of receptor endocytosis. Furthermore, we isolated γ-aminobutylic acid A receptor-binding protein (GABARAP) as a specific binding partner for Ost-III, which inhibits the activity of Ost-III. 3. Analysis of physiological roles of phospholipase Cε in the mouse. 4. Analysis of physiological roles of the guanine nucleotide exchange factos for Rap1, RA-GEF-1 and RA-GEF-2, in the mouse: We generated RA-GEF-1 KO and RA-GEF-2 KO mice. RA-GEF-1 KO mice died by E9.5 due to deficiencies in vascular formation. RA-GEF-2 mice appeared healthy, but tumor necrosis factor-a-dependent integrin activation and cell adhesion was severely impaired in their splenocytes, suggesting a role for RA-GEF-2 in Rap1-dependent integrin activation.

  • Research Products

    (12 results)

All 2007 2006 2005

All Journal Article (10 results) Book (2 results)

  • [Journal Article] The M-Ras-RA-GEF-2-Rap1 pathway mediates tumor necrosis factor-α-dependent regulation of integrin activation in splenocytes2007

    • Author(s)
      Yoko Yoshikawa
    • Journal Title

      Mol. Biol. Cell (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The M-Ras-RA-GEF-2-Rap1 pathway mediates tumor necrosis factor-a-dependent regulation of integrin activation in splenocytes2007

    • Author(s)
      Yoko Yoshikawa
    • Journal Title

      Mol. Biol. Cell (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Phospholipase Cε guanine nucleotide exchange factoractivity and activation of Rap12007

    • Author(s)
      Takaya Satoh
    • Journal Title

      Methods Enzymol. 407

      Pages: 281-290

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Ras and Rap1 activation of phospholipase Cε lipaseactivity2007

    • Author(s)
      Hironori Edamatsu
    • Journal Title

      Methods Enzymol. 407

      Pages: 99-107

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The signaling network of Ras family and Rho family GTP-binding proteins in mammalian cells2007

    • Author(s)
      Takaya Satoh
    • Journal Title

      Cellular Signaling and Apoptosis Research (Alex R. Demasi, ed) (Nova Science Publishers, Hauppauge, NY, USA) (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Phospholipase Cε guanine nucleotide exchange factor activity and activation of Rap12006

    • Author(s)
      Takaya Satoh
    • Journal Title

      Methods Enzymol. 第407巻

      Pages: 281-290

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Ras and Rap1 activation of phospholipase Cε lipase activity2006

    • Author(s)
      Hironori Edamatsu
    • Journal Title

      Methods Enzymol. 第407巻

      Pages: 99-107

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ACK12005

    • Author(s)
      Takaya Satoh
    • Journal Title

      The Alliance for Cellular Signaling-Nature Signaling Gateway Molecule Page

      Pages: A000186

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Requirement of activated Cdc42-associated kinase (ACK) for survival of v-Ras-transformed mammalian cells2005

    • Author(s)
      Alam Nur-E-Kamal
    • Journal Title

      Mol. Cancer Res. 第3巻 第5号

      Pages: 297-305

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Requirement of activated Cdc42-associated kinase (ACK) for survival of v-Ras-transformed mammalian cells2005

    • Author(s)
      Alam Nur-E-Kamal
    • Journal Title

      Mol. Cancer Res. 3-5

      Pages: 297-305

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Cellular Signaling and Apoptosis Research2007

    • Author(s)
      Takaya Satoh
    • Publisher
      Nova Science Publishers, Hauppauge, NY, USA(in press)
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] バイオ研究マスターシリーズ「シグナル伝達集中マスター」2005

    • Author(s)
      佐藤孝哉
    • Total Pages
      130
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2008-05-27  

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