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1991 Fiscal Year Final Research Report Summary

Regulation of lymphocyte phospholipase C activity by a low molecular weight GTP-binding protein and its physiological role

Research Project

Project/Area Number 02670990
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionUniversity of Tokyo

Principal Investigator

TOYOSHIMA Satoshi  University of Tokyo, Faculty of Pharmaceutical Sciences, Associated Professor, 薬学部, 助教授 (40092283)

Project Period (FY) 1990 – 1991
KeywordsPhospholipase C / Butulinum ADP-ribosyltransferase / Lymphocyte activation / T cell antigen receptor / MRL / lpr mouse / low molecular weight GTP-binding protein
Research Abstract

As reported previously, there is a low molecular weight GTP-binding protein(G21K)in calf thymocytes which is associated with not only physically but also functionally with soluble phosphoinositide-specific phospholipase C(PLC). In the present study, its physiological role was investigated and following results were obtained.
1. G21K was found to be ADP-ribosylated by ADP-ribosyltransferase from Clostridum botulinum type C strain and ^<32>P -ADP-ribosylated G21K was easily identified on two dimensional gel electrophoresis.
2. G21K was also detected in mouse thymocytes.
3. Botulinum ADP-ribosyltransferase induced an increase of inositol phosphates(PLC)formation in mouse thymocyte membranes. Incubation of electropermeabilized mouse thymocytes with the enzyme also caused an inprease of IPs formation in the cells. These results suggest that the stimulation of PLC was related to ADP-ribosylation of G21K by the enzyme.
4. G21K was found to be associated with T cell antigen receptor(TCR)/CD3 complex in mouse thymocytes. This result suggests that G21K plays some important role in the T cell activation pathway via TCR/CD3 complex.
5. It was found that very little amounts of G21K were associated with Con A receptor in T cells of autoimmune model mouse, MRL/Ipr. As reported previously, MRL/Ipr T cells hardly respond to Con A and an increase of phosphoinositide turnover is not observed in MRL/Ipr T cells stimulated with Con A. However, Con A binding to the receptor is normal and stimulation of G-protein by GTPYS induces PLC activation. These results suggest that the coupling of Con A-receptor and the G-protein is abnormal.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] P.Wang: "Roles of phospholipase C and GTP-binding proteins in lymphocyte activation." J.Pharmacobio-Dyn.13. S-105 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Toyoshima: "Purification and partial amino acid sequences of phosphoinoitide-specific phospholipase C of Drosophila eye." J.Biol.Chem.265. 14842-14848 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] P.Wang: "Low-molecular weight GTP-binding proteins servng as ADP-ribosylation substrate for ADP-ribosyltransferase form Clostridium botulinum and their relation to phosphoinositides metabolism in thymocytes." J.Biochem.108. 879-885 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 豊島 聰: "各種細胞における細胞内情法伝達系の異常ーリンパ球" Clinical Neuroscience. 9. 870-872 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 豊島 聰: "ホスホリパ-ゼCの活性化とG蛋白質" 蛋白質核酸酵素. 36. 280-289 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] P. Wang: "Roles of phospholipase C and GTP-binding proteins in lymphocyte activation." J. Pharmacobio-Dyn.13. s-105 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Toyoshima: "Purification and partial amino acid sequences of phosphoinositide-specific phospholipase C of Drosophila eye." J. Biol. Chem.265. 14842-14848 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] P. Wang: "Low-molecular weight GTP-binding proteins syrving as ADP-ribosylation substrate for ADP-ribosyltransferase from Clostridium botulinum and their relation to phosphoinositides metabolism in thymocytes." J. Biochem.108. 87-885 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Toyoshima: "Abnormality of cellular signal transduction systems in various cells." Clinical Neuroscience. 9. 870-872 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Toyoshima: "Activation of phospholipase C and G proteins." Protein, Nucleic acid and Enzyme. 36. 280-289 (1991)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1993-03-16  

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