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Studies on intracellular signal transduction through phospholipase D

Research Project

Project/Area Number 09470032
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionKobe University

Principal Investigator

NAKAMURA Shun-ichi  School of Medicine, Kobe University Professor, 医学部, 教授 (40155833)

Co-Investigator(Kenkyū-buntansha) KIKKAWA Ushio  Biosignal Research Center, Kobe University Professor, 教授 (40150354)
YOSHIDA Kimihisa  School of Medicine, Kobe University Research Associate, 医学部, 助手 (50263372)
黒田 俊一  神戸大学, バイオシグナル研究センター, 助教授 (60263406)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥5,500,000 (Direct Cost: ¥5,500,000)
KeywordsSignal transduction / Phospholipase D / G_<M2> activator / G-protein / ADP-ribosylation factor / G_<M2> gangliosidosis / G蛋白質 / 活性化因子
Research Abstract

The hydrolysis of phosphatidylcholine by phospholipase D (PLD) is caused by a wide variety of external signals, and is now thought to generate several lipid messengers or mediators such as phosphatidic acid.
To date, some of small molecular weight G-proteins including ADP-ribosylation factor (ARF) is known to involve in the activation of PLD, although precise mechanism of the enzyme regulation remains to be elucidated. In the series of the present research, we have found that PLD is activated by a heat-stable factor found in rat kidney cytosol. The factor was purified to near homogeneity by a sequential column chromatography. The purified factor was a protein with an apparent molecular mass of 23 kDa on SDS-PAGE.The factor itself was weak to activate PLD partially purified from rat kidney. The factor, however, potently (10 fold) stimulated PLD in a synergistic manner with ARF.
Amino acid sequences of the peptides derived from the purified factor treated : with lysylendpeptidase were almost identical (87 %) with the corresponding sequences of mouse G_<M2> ganglioside activator whose deficiency is known to result in AB-variant of G_<M2> gangliosidosis. The purified factor indeed had the G_<M2> ganglioside activator activity, i.e. the enhancement of conversion of G_<M2> to G_<M3> ganglioside by beta-hexosaminidase A.
These results strongly suggest that G_<M2> ganglioside activator controls the metabolism of both phosphatidylcholine and gangliosides, and may implicate in the signaltransduction whose impairment is closely associate with G_<M2> gangliosidosis.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Kadotani,M.: "Characterization of Tyrosine-Phosphorylated δ Isoform of Protein Kinase C Isolaed from Chinese Hamster Ovary Cells." J.Biochem.121. 1047-1053 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshida,H.: "Isolation and properties of a novel phospholipase A from rat brain that hydrolyses fatty acids at sn-1 and sn-2 positions." Annals Clin.Biochem.35. 295-301 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Akisue,T.: "Purification of a heat-stable activator protein for ADP-ribosylation factor-dependent phospholipase D." FEBS Lett.422. 108-112 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakamura,S.: "Requirement of G_<M2> ganglioside activator for phospholipase D activation" Proc.Natl.Acad.Sci.USA. 95. 12249-12253 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kadotani, M.: "Characterization of tyrosine-phosphorylated delta isoform of protein kinase C isolated from chinese hamster ovary cells." J.Biochem.121. 1047-1053 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshida, H.: "Isolation and properties of novel phospholipase A from rat brain that hydrolyzes fatty acids at sn-1 and sn-2 positions." Annals Clinical Biochem.35. 295-301 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Akisue, T.: "Purification of a heat-stable activator for ADP-ribosylation factor-dependent phospholipse D." FEBS Lett.422. 108-112 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakamura, S.: "Requirement of G_<M2> ganglioside activator for phospholipase D activation." Proc.Natl.Acad.Sci.USA. 95. 12249-12253 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshida,H.: "Isolation and properties of a novel phospholipase A from rat brain that hydrolyses fatty acids at sn-1 and sn-2 positions." Annals Clin.Biochem.35. 295-301 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Akisue,T.: "Purfication of a heat-stable activator protein for ADP-ribosylation factor-dependent phospholipase D." FEBS Lett.422. 108-112 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakamura,S.: "Requirement of G_<M2> ganglioside activator for phospholipase D activation" Proc.Natl.Acad.Sci.USA. 95. 12249-12253 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kadotani,M.: "Characterization of Tyrosine-Phosphorylated δ Isoform of Protein Kinase C Isolated from Chinese Hamster Ovary Cells." J. Biol Chem.121. 1047-1053 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida,H.: "Isolation and properties of a novel phospholipase A from rat brain that hydrolyzes fatty acids at sn-1 and sn-2 positions." Annals Clin. Biochem. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Akisue,T.: "Purification of heat-stable activator protein for ADP-ribosylation factor-dependent phospholipase D." FEBS Lett.(in press).

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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