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1998 Fiscal Year Final Research Report Summary

Physiological functions of a novel family of nucleotide-metabolizing enzymes

Research Project

Project/Area Number 09480160
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

KATADA Toshiaki  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Dept.of Physiol.Chem., Professor, 大学院・薬学系研究科, 教授 (10088859)

Co-Investigator(Kenkyū-buntansha) HOSHINO Shin-ichi  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Dept.of Phy, 大学院・薬学系研究科, 助手 (40219168)
NISHINA Hiroshi  The University of Tokyo, Graduate School of Pharmaceutical Sciences, Dept.of Phy, 大学院・薬学系研究科, 助教授 (60212122)
Project Period (FY) 1997 – 1998
KeywordsCD38 / ecto-enzyme / NADase / cyclic ADP-ribose / retinoic acid / signal transduction
Research Abstract

Ecto-form NADase activity induced by retinoic acid(RA)in HL-60 cells is due to CD38, which has an amino acid sequence homologous to Aplysia ADP-ribosyl cyclase. CD38 catalyzes not only the hydrolysis of NAD^+, but also the formation and hydrolysis of cyclic ADP-ribose (cADPR), that is a novel mediator or modulator of Ca^<2+> release from intracellular Ca^<2+> stores. In the present study, we investigated the functions and properties of CD38 and its related ecto-enzyme, PC-1.1. Stimulation of RA-differentiated HL-60 cells with anti-CD38 monoclonal antibodies induced rapid tyrosine phosphorylation of cellular proteins including the c-cbl proto-oncogene product, pl20^<C-Cbl>. Superoxide formation in response to formyl-Met-Leu-Phe was markedly enhanced by the anti-CD38 mAbs. Fcgamma-II receptors appeared to be involved in the signal transduction pathway mediated through the anti-CD38 mAb-induced tyrosine phosphorylation. 2. CD38 was abundantly present in rat brain in addition to lymphocytes. In primary culture of rat glial and neuronal cells, CD38 was most abundantly observed in astrocyte cell surface. Confocal laser microscopic analysis revealed that immunoreactive CD38 and the enzyme activity were localized on the cell surface of astrocytes. The cell-surface CD38 was rapidly inactivated upon the addition of the enzyme substrates to the cultured astrocytes.
3. An RA response element (RARE) consisting of two direct-repeated TGACCT-like hexamer motifs with a 5-nucleotide spacer was found to be located in the first intron of CD38 gene. This RARE interacted with heterodimer composed of RA receptor and retinoid X receptor. Thus, the RA-induced expression of human CD38 gene was demonstrated to be mediated through the RARE located in the first intron.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] S.Hoshino,et al.: "Mapping of the catalytic and epitopic sites of human CD38/NADase to a functional domain in the carboxy terminus." J.Immunol.158. 741-747 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Tsujimoto,et al.: "Potentiation of chemotactic peptide-induced superoxide generation by CD38 ligation in human myeloid cell lines." J.Biochem.121. 949-956 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Inoue,et al.: "Protein-tyrosine phosphorylation by IgG1-subclass CD38 monoclonal antibodies is mediated through stimulation of the FcγII receptors in human myeloid cell lines." J.Immunol.159. 5226-5232 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H.Kishimoto,et al.: "Molecular mechanism of human CD38 gene expression by retinoic acid : Identification of retinoic acid response element in the first intron." J.Biol.Chem.273. 15429-15434 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] O.Scruel,et al.: "Effects of D-glucose and starvation upon the cyclic ADP-ribose content of rat pancreatic islets." Mol.Biol.Int.45. 783-790 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Katada,et al.: "Enzymic and signal transduction properties of CD38/NADase and PC-1/phosphodiesterase." Chemical Immunology. (印刷中). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Hoshino, I.Kukimoto, K.Kontani, S.Inoue, Y.Kanda, F.Malavasi & T.Katada: "Mapping of the catalytic and epitopic sites of human CD38/NADase to a functional domain in the carboxy terminus." J.Immunol.158. 741-747 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Tsujimoto, K.Kontani, S.Inoue, S.Hoshino, O.Hazeki, F.Malavasi & T.Katada: "Potentiation of chemotactic peptide-induced superoxide generation by CD38 ligation in human myeloid cell lines." J.Biochem.121. 949-956 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Inoue, K.Kontani, N.Tsujimoto, Y.Kanda, N.Hosoda, S.Hoshino, O.Hazeki, & T.Katada: "Protein-tyrosine phosphorylation by IgG1-subclass CD38 monoclonal antibodies is mediated through stimulation of the FcgammaII receptors in human myeloid cell lines." J.Immunol.159. 5226-5232 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Kishimoto, S.Hoshino, M.Ohmori, K.Kontani, H.Nishina, M.Suzawa, S.Kato, & T.Katada: "Molecular mechanism of human CD38 gene expression by retinoic acid : Identification of retinoic acid response element in the first intron." J.Biol.Chem.273. 15429-15434 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] O.Scruel, T.Wada, K.Kontani, A.Sener, T.Katada, & W.J.Malaisse: "Effects of D-glucose and starvation upon the cyclic APD-ribose content of rat pancreatic islets.Biochem." Mol.Biol.Int.45. 783-790 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Katada, K.Kontani, T.Wada, N.Hosoda, S.Hoshino, & H.Nishina: "Enzymic and signal transduction properties of CD38/NADase and PC-1/phosphodiesterase." Chemical Immunology. (in press). (1999)

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

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Published: 1999-12-08  

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