• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Physiological functions of the cell surface antigen CD38

Research Project

Project/Area Number 09044268
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo (Graduate School of Pharmaceutical Sciences)

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) KAPIL Mehta  米国, テキサス大学・アンダーソン癌センター, 教授
FABIO Malava  イタリア, トリノ大学・医学部, 教授
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)
MALAVASI Fabio  The University of Torino, Dept.of Genetics, Biology and Biochemistry, Laboratory
MEHTA Kapil  The University of Texas, MD Anderson Cancer Center, Dept.of Bioimmunotherapy, Pr
櫨木 修  東京大学, 大学院・薬学系研究科, 助教授 (80142751)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywordscyclin ADP-ribose / CD38 / ecto-enzyme / NADase / retinoic acid / signal transduction / リンパ球 / 細胞内陥入
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 obtained the following findings. 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, p12O^<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 antiCD38 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 directrepeated 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.

Report

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

    (23 results)

All Other

All Publications (23 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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Inoue, et al.: "Protein-tyrosine phosphorylation by IgGl-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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Hosino, 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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Inoue, K.Kontani, N.Tsujimoto, Y.Kanda, N.Hosoda, S.Hoshino, O.Hazeki, & T.katada: "Protein-tyrosine phosphorylation by IgGl-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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Kisimoto, S.Hoshino, M.Ohori, 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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] O.Scruel, T.Wada, K.Kontani, A.Sener, T.Katada, & W.J.Malaisse: "Effects of Dglucose and starvation upon the cyclic ADP-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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Related Report
      1998 Annual Research Report
  • [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)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Sasaki,et al.: "Activation of c-Jun N-terminal kinase(JNK)by lysophosphatidic acid in Swiss 3T3 fibroblasts." J.Biochem.124. 934-939 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T:Katada,et al.: "Enzymic and signal transduction properties of CD38/NADase and PC-1/phosphodiesterase." Chemical Immunology. (印刷中) (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Katada,et al.: "Synergistic activation of a family of phosphoinositide 3-kinase via G-protein coupled and tyrosine kinase-related receptors." Chemistry and Physics of Lipids. (印刷中) (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 紺谷圏二 他: "NAD代謝とサイクリックADP-リボース" 化学と生物. 36. 497-503 (1998)

    • Related Report
      1998 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] W. J. Malasisse, et al.: "Cyclic ADP-ribose measurements in rat pancreatic islets." Biochem. Biophys. Res. Commun.231. 546-548 (1997)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] M. Masuda, et al.: "Oscillation of ADP-ribosyl cyclase activity during the cell cycle and function of cyclic ADP-ribose in a unicellular organism, Euglena gracilis." FEBS Lett.405. 104-106 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S. Inoue, et al.: "Protein-tyrosine phosphorylation by IgG1-subclas CD38 monoclonal antibodies is mediated through stimulation of the FcγII receptors in hyman myeloid cell lines." J. Immunol.159. 5226-5232 (1997)

    • Related Report
      1997 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi