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1996 Fiscal Year Final Research Report Summary

Studies on Functions of bioactive phospholipids

Research Project

Project/Area Number 06304050
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section総合
Research Field Structural biochemistry
Research InstitutionGIFU UNIVERSITY

Principal Investigator

NOZAWA Yoshinori  GIFU UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (10021362)

Co-Investigator(Kenkyū-buntansha) SIMIZU Takao  TOKYO UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (80127092)
IKEZAWA Hiroo  NAGOYA CITY UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (40080163)
INOUE Keizo  TOKYO UNIVERSITY,FACULTY OF PHARMACEUTICAL SCIENCES,PROFESSOR, 薬学部, 教授 (30072937)
KANOH Hideo  SAPPORO MEDICAL UNIVERSITY SCHOOL OF MEDICINE,PROFESSOR, 教授 (70045475)
NISHIJIMA Masahiro  NATIONAL INSTITUTE OF HEALTH, THE HEAD, 細胞化学部, 部長 (60072956)
Project Period (FY) 1994 – 1996
KeywordsPhospholipases (A2, C,D) / Bioactive phospholipid / PAF-receptor / PAF-acetylhydrolase / GPI-anchor / PA phosphohydrolase / PIP2-binding protein
Research Abstract

(1) PLD was synergistically activated by PKCalpha and RhoA.Rat PLD2 cDNA was cloned and mRNA levels of rPLD1a, 1b and 2 were observed to change during proliferation and differentiation (Nozawa). (2) cDNA of PAF-acetylhydrolase of guinea-pig blood plasma was isolated and the primary structure of the enzyme was determined (Nojima). (3) The CD14 was found to be the endotoxin (LPS) receptor. The signaling through LPS receptor requires PC breakdown by PLD (Nishijima). (4) The PLCdelta4 cDNA was cloned and its mRNA was expressed in the regenerating rat liver cell nuclei. A downstream molecules of Ash/Grb2 was PIP2 phosphatase (Takenawa). (5) DGKdelta and PAP2a, b were cloned. PAP2a was identified to be a Wunen homologue and PAP2b was Dri gene (Kanoh). (6) The image analysis with fluorescence microscope has shown that PS and some cytosolic factor(s) were required for the PS transfer to Golge bodies (Ohki). (7) PAF-acetylhydrolase was found to be composed of 3 subunits (alpha1, alpha2=catalytic subunits). beta subunit is the product of LIS-1 gene of Miller-Dieker syndrome (Inoue). (8) The amino acid sequences of the N-terminal and internal part of amino peptidase N were determined. GPI-anchored protein(s) was found in Sulfolobus (Ikezawa). (9) Expression of the intestinal phospholipase B-cDNA revealed that this enzyme was a novel serine esterase (Okamoto). (10) Sphingosine showed structural specific inhibition of DNA polymerase. PLA_2 purified from the chromatin fraction of rat ascitic hapatoma was 17kDa PLA_2II which was specifically localyzed (Koizumi). (11) It was demonstrated that 2 splicing variants of PAF-receptor genes were present and that leucocyte regulated by distinct promotors. Physiological functions were examined by using knock-out mice (Shimizu).

  • Research Products

    (58 results)

All Other

All Publications (58 results)

  • [Publications] Y. Banno: "Thrombin-mediated phosphoinositide hydrolysis in CHO cells overexpressing phospholipase C-δ1" J. Biol. Chem.269. 15846-15852 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Ohashi: "Peripheral blood cells are predominantly chimeric of affected and normal cells in patients with paroxysmal nocturnal hemoglobinuria" Blood. 83. 853-859 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Hattori: "Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase" Nature. 370. 216-218 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Kai: "Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in human retina with a truncated and inactive enzyme expression in most other human cells" J. Biol. Chem.269. 18492-18498 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Asano: "Purification and characterization of nuclear phospholipase C specific for phosphoinositides" J. Biol. Chem.269. 12360-12366 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Tanaka: "C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the src homology 3 domains of crk and grb2/ash proteins" Proc. Natl. Acad. Sci.91. 3443-3447 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Okutani: "Grb2/Ash binds directly to tyrosine kinase 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact vells" J. Biol. Chem.269. 31310-31314 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Bito: "Functional coupling of a rat hippocampal somatostatin receptor to inhibition of adenylate cyclase, activation of arachidonate release and MAP kinase" J. Biol. Chem.269. 12727-12730 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Gotoda: "Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the α-tocopherol-transfer protein" New Eng. J. Med.333. 1313-1318 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J. C. Hay: "ATP-dependent inositide phosphorylation required for Ca^<2+>-activated secretion" Nature. 374. 173-177 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Fukasawa: "Chinese hamster ovary cells expressing a novel type of acetylated low density lipoprotein receptor" J. Biol. Chem.270. 1921-1927 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] I. Wada: "Chaperon function of calreticulin when expressed in the endoplasmic reticulum as the membrane-anchored and soluble forms" J. Biol. Chem.270. 20298-20304 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Ouahchi: "Ataxia with isolated vitamin E deficiency is caused by mutations in the α-tocopherol transfer protein" Nature Genet.9. 141-145 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Hanada: "Both sphingolipids and cholesterol participate in the detergent insolubilityof alkaline phosphatase a glycosylphosphatidylinositol-anchored protein, in mammalian membranes" J. Biol. Chem.270. 6254-6260 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Banno: "Endogenous cleavage of phospholipase β3 agonist-induced calpain activation in human platelets" J. Biol. Chem.270. 4318-4323 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Mutoh: "Tissus-specific response of the human platelet-activating factor receptor gene to retinoic acid and thyroid hormone by alternative promoter usage" Proc. Natl. Acad. Sci.93. 774-779 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Ohguchi: "Regulation of membrane phospholipase D by protein kinase C in HL60 cells. Synergistic action of small GTP-binding protein RhoA" J. Biol. Chem. 271. 4366-4373 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Yokomizo: "cDNA cloning, expression, and mutagenesis study of leukotriene B4 12-hydroxy-dehydrogenase" J. Biol. Chem.271. 2844-2850 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Kai: "Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type 2) bound to plasma membranes" J. Biol. Chem.271. 18931-18938 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Moriya: "PDGF activates protein kinase C ε through redundant and independent signaling pathway involving phospholipase C γ or phosphatidylinositol 3-kinase" Proc. Natl. Acad. Sci.93. 151-155 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Tasaka: "Targeted mutagenesis of acyl-lipid desaturases in Synechocystis : Evidencefor the important roles of poly-unsaturated membrane lipids in growth, respiration and photosynthesis" EMBO J.15. 6416-6425 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Emoto: "Redistribution of phosphatidylethanolamine at the cleavage furrow of dividing cells during cytokinesis" Proc. Natl. Acad. Sci.93. 12867-12872 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Miki: "A novel actin-depolymerizing protein N-WASP regulates the cortical cytoskeletal rearrangement in a PIP2 dependent manner at the downstream of tyrosine kinase" EMBO J.15. 5326-5335 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y-S. Ho: "Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer" Nature. 385. 89-93 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Higashida: "Progress in Brain Reserch" (ed. Kruger, L.). Elsevier Science Publisher B. V., 15 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Nakashima: "Handbook of Experimental Pharmacology ″Platelets and their factors″" Platelet phospholipase C, D (Bruchhausen, V. and Walter, U., eds.) Springer-Verlag, 15 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Takenawa: "Advance in Pharmacol vol. 36 Intracellular Signal Transduction" Signal transductions of SH2/SH3 : Ash/Grb2 downstream signals (eds. Narin and Hidaka), 14 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Nakashima: "Advances in Molecular and Cell Biology Series Vol. 17 The Platelet" Role of signal-transducing phospholipase A2, C and D in platelet activation (Lapetina EG, ed.). JAI Press Inc, 21 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Kanoh: "Guidebook on calcium binding proteins" Diacylglycerol kinase (ed. by Celio, M. R.) Oxford University Press (in press), (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Banno: "Thrombin-mediated phosphoinositide hydrolysis in CHO cells overexpressing phospholipase C-delta1" J.Biol.Chem. 269. 15846-15852 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Ohashi: "Peripheral blood cells are predominantly chimeric of affected and normal cells in patients with paroxysmal nocturnal hemoglobinuria" Blood. 83. 853-859 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Hattori: "Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor acetylhydrolase" Nature. 370. 216-218 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Kai: "Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in human retina with a truncated and inactive enzyme expression in most other human cells" J.Biol.Chem.269. 18492-18498 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Asano: "Purification and characterization of nuclear phospholipase C specific for phospho-inositides." J.Biol.Chem.269. 12360-12366 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Tanaka: "C3G,a guanine nucleotide-releasing protein expressed ubiquitously, binds to the src homology 3 domains of crk and grb2/ash proteins" Proc.Natl.Acad.Sci.91. 3443-3447 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Okutani: "Grb2/Ash binds directly to tyrosine kinase 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact vells." J.Biol.Chem.269. 31310-31314 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Bito: "Functional coupling of a rat hippocampal somatostatin receptor to inhibition of adenylate cyclase, activition of arachidonate release and mitogen-activated (MAP) kinase" J.Biol.Chem.269. 12727-12730 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Gotoda: "Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the alpha-tocopherol-transfer protein" New Eng.J.Med.333. 1313-1318 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.C.Hay: "ATP-dependent inositide phosphorylation required for Ca^<2+>-activated secretion" Nature. 374. 173-177 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Fukasawa: "Chinese hamster ovary cells expressing a novel type of acetylated low density lipoprotein receptor" J.Biol.Chem.270. 1921-1927 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] I.Wada: "Chaperon function of calreticulin when expressed in the endoplasmic reticulum as the membrane-anchored and soluble forms" J.Biol.Chem.270. 20298-20304 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Ouahchi: "Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein" Nature Genet.9. 141-145 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hanada: "Both sphingolipids and cholesterol participate in the detergent insolubility of alkaline phosphatase a glycosylphosphatidylinositol-anchored protein, in mammalian membranes." J.Biol.Chem.270. 6254-6260 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Banno: "Endogenous cleavage of phospholipase beta3 by agonist-induced calpain activation in human platelets" J.Biol.Chem.270. 4318-4323 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Mutoh: "Tissue-specific response of the human platelet-activating factor receptor gene to retinoic acid and thyroid hormone by alternative promoter usage" Proc.Natl.Acad.Sci.93. 774-779 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Ohguchi: "Regulation of membrane phospholipase D by protein kinase C in HL60 cells. Synergistic action of small GTP-binding protein RhoA" J.Biol.Chem.271. 4366-4373 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Yokomizo: "cDNA cloning, expression, and mutagenesis study of leukotriene B4 12-hydroxy-dehydrogenase" J.Biol.Chem.271. 2844-2850 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Kai: "Identification and cDNA cloning of 35-kDa phosphatidic acid phosphatase (type 2) bound to plasma membranes." J.Biol.Chem.271. 18931-18938 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Moriya: "PDGF activates protein kinase Cepsilon through redundant and independent signaling pathway involving phospholipase Cgamma or phosphatidylinositol 3-kinase" Proc.Natl.Acad.Sci.93. 151-155 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Tasaka: "Targeted mutagenesis of acyl-lipid desaturases in Synechocystis : Evidence for the important roles of polyunsatureted membrane lipids in growth, respiration and photosynthesis" EMBO J.15. 6416-6425 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Emoto: "Redistribution of phosphatidylethanolamine at the cleavage furrow of dividing cells during cytokinesis" Proc.Natl.Acad.Sci.93. 12867-12872 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Miki: "A novel actin-depolymerizing protein N-WASP regulates the cortical cytoskeletal rearrangement in a PIP_2 dependent manner at the downstream of tyrosine kinase" EMBO J.15. 5326-5335 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y-S.Ho: "Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer" Nature. 385. 89-93 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Higashida (ed.Kruger, L.): Elsevier Science Publisher B.V.Progress in Brain Research, 15 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Nakashima: Platelet phospholipase C, D (Bruchhausen, V.and Walter, U., eds.) Springer-Verlag. Handbook of Experimental Pharmacology Platelets and factors, 15 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Takenawa: Signal transductions of SH2/SH3 : Ash/Grb2 downstream signals (eds. Naarin and Hidaka). Advance in Pharmacol vol.36, Intracellular Signal Transduction, 14 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Nakashima: Role of signal-transducing phospholipase A2, C,D in platelet activation (Lapetina E.G., ed.) JAI Press Inc. Advances in Molecular and Cell Biology Series Vol.17 The Platelet, 21 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Kanoh: Diacylglucerol kinase (ed.by Celio, M.R.) Oxford University Press. Guidebook on calcium binding proteins (in press), (1997)

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

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Published: 1999-03-09  

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