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Analysis of NAD-cleavage Enzymes Involved in Signal Transduction System

Research Project

Project/Area Number 06454651
Research Category

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

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

Principal Investigator

KATADA Toshiaki  The University of Tokyo, Faculty of Pharmaceutical Sciences, Dept.of Physiol.Chem., Professor, 薬学部, 教授 (10088859)

Co-Investigator(Kenkyū-buntansha) HOSHINO Shin-ichi  The University of Tokyo, Faculty of Pharmaceutical Sciences, Dept.of Physiol.Che, 薬学部, 助手 (40219168)
HAZEKI Osamu  The University of Tokyo, Faculty of Pharmaceutical Sciences, Dept.of Physiol.Che, 薬学部, 講師 (80142751)
仁科 博史  東京工業大学, 生命理工学部, 助手 (60212122)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1995: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1994: ¥4,900,000 (Direct Cost: ¥4,900,000)
KeywordsNAD / cyclic ADP-ribose / NAD-cleavage enzyme / ADP-ribosyl cyclase / CD38 / calcium ion / signal transduction
Research Abstract

The human cell surface antigen CD38, which has an amino acid sequence homologous to Aplysia ADP-ribosyl cyclase, is a 46-kDa type II glycoprotein with a single-transmembrane domain. We previously demonstrated that the extracellular domain of CD38 exhibits NAD^+ glycohydrolase (NADase) activity and that the ecto-form NADase activity induced by all-trans retinoic acid (RA) in HL-60 cells is due to CD38 (Kontani, K.et al., J.Biol.Chem.268 : 16895,1993). CD38 catalyzes not only the hydrolysis of NAD^+, but also the formation and hydrolysis of cyclic ADP-ribose, which is a novel candidate that mediates Ca^<2+> release from intracellular Ca^<2+> stores. In the present study, we obtained the following findings. 1. Besides these enzyme activities, CD38 had the ability to bind hyaluronate. 2. Stimulation of RA-differentiated HL-60 cells with anti-CD38 monoclonal antibody (mAb) induced rapid tyrosine phosphorylation of cellular proteins with the molecular weight of 120,000,87,000 and 77,000. One of the prominent phosphorylated proteins was identified as the c-cbl proto-oncogene product, p120^<c-cbl>.3. Superoxide formation in response to formyl-Met-Leu-Phe was markedly enhanced by the anti-CD38 mAb in the differentiated HL-60 cells. 4. Zn^<2+> directly interacted with CD38 to convert its catalytic properties from NADase to ADP-ribosyl cyclase, probably due to prevention of the access of water molecule to an intermediate of the enzyme-substrate complex. 5. Although the expression of CD38 mRNA was mediated through nuclear RA receptors, a negative regulatory element present in the first intron of CD38 gene appeared to be involved in the RA-induced expression of CD38 mRNA in HL-60 cells.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Hiroshi Nishina: "Cell surface antigen CD38 identified as ecto-enzyme of NAD glycohydrolase has hyaluronate-binding activity" Biochem. Biophys. Res. Commun.203. 1318-1323 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tomohiko Maehama: "ADP-ribosylarginine glycohydrolase catalyzing the release of ADP-ribose from the cholera toxin-modified α-subuinits of GTP-binding proteins." J. Biochem.116. 1134-1138 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kiyoshi Inageda: "Enzyme property of Aplysia ADP-ribosyl cyclase:Comparison with NAD glycohydrolase of CD38 antigen." J. Biochem.117. 125-131 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tomohiko Maehama: "NAD^+-dependent ADP-ribosylatin of T-lymphocyte alloantigen RT6.1 reversibly proceeding in intact rat lymphocytes." J. Biol. Chem.270. 22747-22751 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Katsunobu Takahashi: "Accumulation of cyclic ADP-ribose measured by a specific radiommunoassay in differentiated human leukemic-HIL-60 cells with all-trnas-retinoic acid." FEBS Lett.371. 204-208 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kenji Kontani: "Tyrosine phosphorylatin of the c-cbl proto-oncogene product mediated by cell surface antigen CD38 in HL-60 cells." J. Biol. Chem.271(in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toshiaki Katada: "Methods in Enzymology Vol. 237, (Heterotrimeric G Proteins; R. Iyengar, ed. )" Academic Press, Inc., 561 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toshiaki Katada: "Bacterial Toxins and Virulence Factors in Disease(J. Moss, B. Iglewski, M. Vaughan and T. A. Tu, eds. )Handbook of Natural Toxins: Vol. 8" Marcel Dekker, Inc., 627 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Nishina, K.Inageda, K.Takahashi, K.S.Hoshino, K.Ikeda, & T.Katada: "Cell surface antigen CD38 identified as ecto-enzyme of NAD glycohydrolase has hyaluronate-binding activity." Biochem.Biophys.Res.Commun.203. 1318-1323 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Maehama, H.Nishina, & T.Katada: "ADP-ribosylarginine glycohydrolase catalyzing the release of ADP-ribose from the cholera toxin-modified alpha-subunits of GTP-binding proteins." J.Biochem.116. 1134-1138 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Inageda, K.Takahashi, K.Tokita, H.Nishina, Y.Kanaho, I.Kukimoto, K.Kontani, S.Hoshino, & T.Katada: "Enzyme property of Aplysia ADP-ribosyl cyclase : Comparison with NAD glycohydrolase of CD38 antigen." J.Biochem.117. 125-131 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Maehama, H.Nishina, S.Hoshino, Y.Kanaho, & T.Katada: "NAD^+-dependent ADP-ribosylation of T-lymphocyte alloantigen RT6.1 reversibly proceeding in intact rat lymphocytes." J.Biol.Chem.270. 22747-22751 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Takahashi, I.Kukimoto, K.Tokita, K.Inageda, S.Inoue, K.Kontani, S.Hoshino, H.Nishina, Y.Kanaho, &T.Katada: "Accumulation of cyclic ADP-ribose measured by a specific radioimmunoassay in differentiated human leukemic HL-60 cells with all-trans-retinoic acid." FEBS Lett.371. 204-208 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Kontani, I.Kukimoto, H.Nishina, S.Hoshino, O.Hazeki, Y.Kanaho, & T.Katada: "Tyrosine phosphorylation of the c-cbl proto-oncogene product mediated by cell surface antigen CD38 in HL-60 cells." J.Biol.Chem.271 : in press. (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Katada, K.Kontani, A.Inanobe, I.Kobayashi, Y.Ohoka, H.Nishina, & K.Takahashi: Purification and separation of closely related members of pertussis toxin-substrate G proteins. [Book] Methods in Enzymology Vol.237, (Heterotrimeric G Proteins ; R.Iyengar, ed.). 131-139 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] T.Katada, T.Iiri, K.Takahashi, H.Nishina & Y.Kanaho: GTP-binding proteins as the substrates of pertussis toxin-catalyzed ADP-ribosylation. [Book] Bacterial Toxins and Virulence Factors in Disease (J.Moss, B.Iglewski, M.Vaughan and T.A.Tu, eds.) Handbook of Natural Toxins : Vol.8. Marcel Dekker, Inc., New York, 459-489 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kiyoshi Inageda: "Enzyme property of Aplysia ADP-ribosyl cyclase:Comparison with NAD glycohydrolase of CD38 antigen." J.Biochem.117. 125-131 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshiharu Ohoka: "Involvement of pertussis toxin-sensitive mechanism in retinoic acid-induced differentiation of human leukemic HL-60 cells." J.Biochem.117. 190-196 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tomohiko Maehama: "NAD^+-dependent ADP-ribosylation of T-lymphocyte alloantigen RT6.1 reversibly proceeding in intact rat lymphocytes." J.Biol.Chem.270. 22747-22751 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Katsunobu Takahashi: "Accumulation of cyclic ADP-ribose measured by a specific radioimmunoassay in differentiated human leukemic HL-60 cells with all-trans-retinoic acid." FEBS Lett.371. 204-208 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hideo Kuribara: "Synergistic activation of rat brain phospholipase D by ADP-ribosylation factor and rhoA p21,and its inhibition by Clostridium botulinum C3 exoenzyume." J.Biol.Chem.270. 25667-25671 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kenji Kontani: "Tyrosine phosphorylation of the c-cbl proto-oncogene product mediated by cell surface antigen CD38 in HL-60 cells." J.Biol.Chem.271(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Toshiaki Katada: "Handbook of Natural Toxins.Vol.8:Bacterial Toxins and Virulence Factors in Disease(J.Moss,B.Iglewski,M.Vaughan and T.A.Tu,eds.)" Marcel Dekker,Inc., 627 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 堅田利明: "GTP結合蛋白質(高井義美、堅田利明、成宮周 編)" 羊土社, 312 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroshi Nishina,et al.: "Cell surface antigen CD38 identified as ecto-enzyme of NAD glycohydrolase has hyaluronate-binding activity." Biochem.Biophys.Res.Commun.203. 1318-1323 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tomohiko Maehama,et al.: "Characterization of butulinum C3-catalyzed ADP-ribosylation of rho proteins and identification of mammalian C3-like ADP-ribosyltransferase." Mol.Cell.Biol.138. 135-140 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Jun-ichi Kawabe,et al.: "Differential activation of adenylyl cyclase by protein kinase C isoenzymes." J.Biol.Chem.269. 16554-16558 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Tomohiko Maehama,et al.: "ADP-ribosylarginine glycohydrolase catalyzing the release of ADP-ribose from the cholera toxin-modified α-subunits of GTP-binding proteins." J.Biochem.116. 1134-1138 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kiyoshi Inageda,et al.: "Enzyme property of Aplysia ADP-ribosyl cyclase:Comparison with NAD glycohydrolase of CD38 antigen." J.Biochem.117. 125-131 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshiharu Ohoka,et al.: "Involvement of pertussis toxin-sensitive mechanism in retinoic acid-induced differentiation of human leukemic HL-60 cells." J.Biochem.117. 190-196 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toshiaki Katada,et al.: "Heterotrimeric G proteins(Methods in Enzymology,Vol.237)" Academic Press,Inc., 561 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 金保安則,堅田利明: "GTP結合蛋白質(宇井理生 編)" メジカルレビュー社, 207 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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