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Functional analysis of regulatory mechanism of G protein signal network

Research Project

Project/Area Number 17370051
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionNara Institute of Science and Technology

Principal Investigator

ITOH Hiroshi  Nara Inst. of Sci. & Tech., Cell Biology, Professor, バイオサイエンス研究科, 教授 (10183005)

Co-Investigator(Kenkyū-buntansha) MIZUNO Norikazu  Nara Inst. of Sci. & Tech., Cell Biology, Assi. Professor, バイオサイエンス研究科, 助手 (90212232)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2006: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2005: ¥8,300,000 (Direct Cost: ¥8,300,000)
KeywordsG protein / Signal transduction / Tyrosine kinase / Neural progenitor cells / Cell migration / Signal amplifier / 低分子量GTP結合タンパク質 / Rho GEF / MAPキナーゼ
Research Abstract

G proteins are composed of a, p, and y subunits, and transmit a variety of signals from G protein-coupled receptors (GPCRs) to intracellular effectors by acting as molecular switch. We demonstrated that the GPCR signaling through Gq and JNK negatively regulates the neural progenitor cell migration. Moreover, we found that Ric-8 and flotillins are a new type of Gq-binding regulatory proteins. Ric-8A promoted the guanine nucleotide exchange of Gαq, and amplified the Gq-mediated cellular responses, such as intracellular Ca mobilization and JNK activation. It was revealed that Ric-8A translocates from cytosol to membrane upon receptor stimulation. The knockdown of flotillins, which are known to be lipid raft maker proteins, by siRNA attenuated the GPCR-induced p38 MAPK activation and tyrosine phosphorylation. Treatment with Src tyrosine kinase inhibitors and cholesterol depleting agent methyl-beta-cyclodextrin also inhibited the GPCR-induced p38 MAPK activation and tyrosine phosphorylation. These lines of evidence suggested that a Gq-coupled receptor activates p38 MAPK through lipid rafts and Src, in which flotillins positively regulates the Gq signaling. Previously, we demonstrated that FRG, a novel RhoGEF for Cdc42, is activated downstream of Gq-coupled receptor. In this research, we found that FRG functions in the signaling pathway downstream CD47 and Src and is involved in the development of axons and dendrites in hippocampal neurons. Another RhoGEF P-Rex1 is activated by G protein βγ subunit and essential for reactive oxygen species (ROS) production in neutrophils. We found that intramolecular domain interaction of P-Rex1 is critical for Gβγ-induced activation and PKA-induced inhibition.

Report

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

    (9 results)

All 2007 2006 2005

All Journal Article (9 results)

  • [Journal Article] The lipid raft proteins flotillins/reggies interact with Gαq and are involved in Gq-mediated p38 mitogen-activated protein kinase activation through tyrosine kinase2007

    • Author(s)
      Y.Sugawara et al.
    • Journal Title

      Cell. Signal. 19

      Pages: 1301-1308

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The lipid raft proteins flotillins/reggies interact with Gαq and are involved in Gq-mediated p38 mitogen-activated protein kinase activation through tyrosine kinase.2007

    • Author(s)
      Y.Sugawara et al.
    • Journal Title

      Cell. Signal. 19 (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ric-8A potentiates Gq-mediated signal transduction by acting downstream of G protein-coupled receptor in intact cells2006

    • Author(s)
      A.Nishimura et al.
    • Journal Title

      Genes Cells 11

      Pages: 487-498

    • 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] CD47 promotes neuronal development through Src- and FRG/Vav2-mediated activation of Rac and Cdc422006

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

      J. Neurosci. 26

      Pages: 12397-12407

    • 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] CD47 promotes neuronal development through Src-and FRG/Vav2-mediated activation of Rac and Cdc422006

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

      J. Neurosci. 26

      Pages: 12397-12407

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ric-8A potentiates Gq-mediated signal transduction by acting downstream of G protein-coupled receptor in intact cells2006

    • Author(s)
      A.Nishimura et al.
    • Journal Title

      Genes Cells 11(in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration2005

    • Author(s)
      N.Mizuno et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA 102

      Pages: 12365-12370

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration2005

    • Author(s)
      N.Mizuno et al.
    • Journal Title

      Proc. Natl. Acad. Sci. USA. 102

      Pages: 12365-12370

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] G protein-coupled receptor signaling through Gq and JNK negatively regulates neural progenitor cell migration2005

    • Author(s)
      N.Mizuno et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102

      Pages: 12365-12370

    • Related Report
      2005 Annual Research Report

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

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