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Phospholipid degradation cascade and protein kinase C for intracellular signaling network.

Research Project

Project/Area Number 05404021
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionKobe University

Principal Investigator

NISHIZUKA Yasutomi  Kobe University, School of Medicine, Professor, 医学部, 教授 (10025546)

Co-Investigator(Kenkyū-buntansha) OGITA Kouji  Kobe University, School of Medicine, Research Associate, 医学部, 助手 (60204103)
ASAOKA Yoshinori  Kobe University, School of Medicine, Associate Prosessor, バイオシグナル研究センター, 助教授 (20222565)
NAKAMURA Shun-ichi  Kobe University, School of Medicine, Associate professor, 医学部, 助教授 (40155833)
KIKKAWA Ushio  Kobe University, Biosignal Research Center, Professor, バイオシグナル研究センター, 教授 (40150354)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥41,200,000 (Direct Cost: ¥41,200,000)
Fiscal Year 1994: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 1993: ¥30,200,000 (Direct Cost: ¥30,200,000)
KeywordsSignal transduction / Protein kinase C / Phospholipase A2 / Phospholipase D / Diacylglycerol / 細胞内情報伝達機構 / ホスホリパーゼA_2
Research Abstract

Protein kinase C plays essential roles in a wide variety of cellular responses. It is accepted that phosphatidylinositol hydrolysis by phospholipase C generates diacylglycerol that is essential to protein kinase C activation. In addition, the hydrolysis of phosphatidylcholine by phospholipae D also produces diacylglycerol through the phosphatidate formation, and arachidonic acid, a product of the hydrolysis of membrane phospholipids by phospholipase A2 reaction, also involves the signal transduction through protein kinase C.
We have shown that the primary products of the phosphatidylcholine hydrolysis by phospholipase A2, cis-unsaturated fatty acids and 2-lysophosphatidylcholine, both appear to serve as enhancer molecules for the diacylglycerol-dependent PKC activation in cell-free enzymatic reaction and for cellular responses. Permeabilized human leukemic cell lines released various unsaturated fatty acids that is potentiated by vanadate and GTP-gS,suggesting the involvement of tyrosine phosphorylation and GTP-binding proteins in the activation of arachidonic acid-non selective phospholipase A2. The results imply that several phospholipases A2, both arachidonic acid-selective and nonselective enzymes, are coupled to receptors for their activation, thereby functioning in the transmembrane control of cellular event.
In contrast, the hydrolysis of phosphatidylcholine by phospholipase D is absolutely requires GTP-gS and uncharacterized factors in the cytosolic fraction. PKC and tyrosine kinases both potentiates the activation of this enzyme. Dynamic change of a wide variety of lipid molecules produced by various phospholipases appears to be critical for the regulation of intracellular event.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Asaoka,Y.: "Potential role of phospholipase A2 in HL-60 cell differentiation to macrophage induced by protein kinase C activation." Proceedings of National Academy of Sciences USA. 90. 4917-4921 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sasaki,Y.: "Potentiation of diacylglycerol-induced activation of protein kinase C by lysophospholipids,subspecies difference." FEBS Lett. 320. 47-51 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsushima,S.: "Protein kinase Cδ-and ε-subspecies in rat central nervous tissues;differential distribution and phorbol ester-induced redistribution in synaptosomes." Neurosci.Res.19. 339-343 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura,S.: "Lipid mediators and protein kinase C activation for intracellular signaling network." J.Biochem.115. 1029-1034 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura,S.: "Protein kinase C for cell signaling:A possible link between phospholipases." Advances in Second Messenger and Phosphoprotein Research. 28. 171-178 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsujishita,Y.: "Regulation of phospholipase A2 in human leukemia cell lines:Its implication for intracellular signaling." Proceedings of National Academy of Sciences USA. 91. 6274-6278 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nishizuka,Y.: "Proteim kinase C and lipid signaling for sustained cellular responses (in press)" FASEB J.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura,S.: "Lipid second messenger and protein kinase C for intracellular signalling,(in press)" Pharmacological Sciences.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Asaoka,Y.: "Intracellular signaling by phospholipid hydrolyais and protein kinase C activation." Biomed.Res.14(Supp12). 93-98 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura,S.: "Protein kinase C and lipid signaling for cellular regulation." Nato/FEBS Symposium Series(Parker,L.ed.)1994 (in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Asaoka,Y.: "Handbook of lipid research" Prenum press(Bell,R.M.,Prescott,S.M.and Exton,J.H.eds) (in press),

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Asaoka, Y.: "Potential role of phosphoipase A2 in HL-60 cell differentiation to macrophage induced by protein kinase activation." Proc.Natal.Acad.Sci.90. 4917-4921 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sasaki, Y.: "Potentiation of diacylglycerol-induced activation of protein kinase C by lysophospholipids, subspecies difference." FEBS Lett.320. 47-51 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura, S.: "Protein kinase C for cell signaling : a possible link between phospholipases." Adv.Second Messenger and Phosphoprotein Res.28. 171-178 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Asaoka, Y.: "Intracellular signalling by phospholipid hydrolysis and protein kinase C activation" Biomedical Res.14. 93-98 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsushima, S.: "Protein kinase C delta- and epsilon-subspecies in rat central nervous tissue." Meuroscience Res.19. 339-343 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura, S.: "Lipid mediator and protein kinase C activation for the intracellular signaling network." J.Biochem.115. 1029-1034 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsujihsa, Y.: "Regulation of phospholipase A2 in human lukemia cell lines : Its implication for intracellular signaling." Proc.Natal.Acad.Sci.91. 6274-6278 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nakamura, S.: "Lipid second messenger and protein kinase C for intracellular signalling." Pharmacol.Rev.(1994). (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nkamura,S.: "Lipid mediators and protein kinase Cactivation for intracellular signaling network." J.Biochem.115. 1029-1034 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tsujishita,Y.: "Regulation of phospholipase A2 in human leukemia cell lines:Its implication for intracellular signaling." Proceedings of National Academy of Sciences USA. 91. 6274-6278 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nishizuka,Y.: "Protein kinase C and lipid signaling for sustained cellular responses" FASEB J.(in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakamura,S.: "Lipid second messenger and protein kinase C for intracellular signalling." Pharmacological Sciences. (in press.).

    • Related Report
      1994 Annual Research Report
  • [Publications] Asaoka,Y.: "Handbook of lipid research" Prenum press(Bell,R.M.,Prescott,S.M.and Exton,J.H.eds)(in press.),

    • Related Report
      1994 Annual Research Report
  • [Publications] Nakamura,S.: "Protein kinase C and lipid signaling for cellular regulation." Nato/FEBS Symposium Series(Parker,L.ed.)(in press.),

    • Related Report
      1994 Annual Research Report
  • [Publications] Asaoka,Y.: "Potential role of phospholipase A_2 in HL-60 cell differentiation to macrophage induced by protein kinase C activation." Proceedings of National Academy of Science USA. 90. 4917-4921 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Nakamura,S.: "Lipid mediators and protein kinase C activation for intracellular signaling network." Journal of Biochemistry. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] Asaoka,Y.: "Intracellular signaling by phospholipid hydrolysis and protein kinase C activation." Biomedical Research. 14 Supplement2. 93-98 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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