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The practicability of phosphatase inhibitors for research reagents.

Research Project

Project/Area Number 03556040
Research Category

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

Allocation TypeSingle-year Grants
Research Field 基礎獣医学
Research InstitutionThe University of Tokyo

Principal Investigator

KARAKI Hideaki  Univ.Tokyo Fac.Agr Prof., 農学部, 教授 (60011912)

Co-Investigator(Kenkyū-buntansha) MAGAE Junji  Tokyo Institute Department of Technology of Bioengineering Associate Prof., 生命理工学部, 講師 (60199643)
SHIOTA Kunio  Univ.Tokyo Fac.Agr Associate Prof., 農学部, 助教授 (80196352)
FUSETANI Nobuhiro  Univ.Tokyo Fac.Agr Prof., 農学部, 教授 (70012010)
HON Masatoshi  Univ.Tokyo Fac.Agr Assistant Prof., 農学部, 助手 (70211547)
OZAKI Hiroshi  Univ.Tokyo Fac.Agr Associate Prof., 農学部, 助教授 (30134505)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥16,300,000 (Direct Cost: ¥16,300,000)
Fiscal Year 1993: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1992: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1991: ¥6,900,000 (Direct Cost: ¥6,900,000)
Keywordsphosphatase / smooth muscle / ion channel / cytoskeleton / ホスファターゼ / 平滑筋 / 海産毒 / ホスファタ-ゼ
Research Abstract

It was known that there are four phosphatase inhibitors, such as okadaic acid, calyculin-A, tautomycin and microcystin-LR.At first, we investigated the effects of these compounds on various types of phosphatase acitivities. okadaic acid and microcystin-LR selectively inhibited type 2A phosphatase purified from bovine cardiac muscle at low concentration. At high concentration, however, these compounds also inhibited type 1 phosphatase purified from turkey gizzard. In contrast, calyculin-A and tautomycin nonselectively inhibited type 1 and type 2A phosphatase. These compounds did not affect on type 2B and 2C phosphatases.
We inivestigated the physiological role of phosphatase on contractile elements, ion channels and cell structure, and clarified that the regulatory phosphatase of contractile elements may have type 1 like characterization for phosphatase inhibitors in smooth muscle, and that calyculin-A may facilitate the opening of the L-type Ca channels through the protein kinase C-dependent phosphorylation system in smooth muscle cells of guinea-pig taenia coli and that the changes in cytoskeletal structure may be caused by disturbing the balance of phosphorylation and dephosphorylation in the culured A10 cells.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] UBUKATA,M: "Absolute configuration of tautomycin,a protein phosphatase inhibitor from a streptomycete." J.Chem.Soc.Perkin Trans. 1. 617-623 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] KOBINATA,K: "RK-397,a new oxo pentaene antibiotic." J.Antibiotics. 46. 1616-1618 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] HOSOYA,N: "Changes in the cytoskeletal structure of cultured smooth muscle cells induced by calyculin-A" J.Cell.Sci.105. 883-890 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] HORI,M: "Mycalolide-B,a novel and specific inhibitor of actomyosin ATPase isolated from marine sponge." FEBS Lett.322. 151-154 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] OSADA,H: "Developments in industrial microbiology series,Microbiol Metabolites,vol.32" Wm.C.Brown Publishers, (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ubutaka, M.: "Absdute configuration of tautomycin, a protein phosphatase inhibitor from a streptomycete." J.Chem.Soc.Perkin Trans. 1. 617-623 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Kobinata, K.: "RK-397, a new oxo pentaene antibiotic." J.Antibiotics. 46. 1616-1618 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hosoya, N.: "Changes in the cytoskeletak structure of cultured smooth muscle cells induced by calyculin-A." J.Cell, Sci.105. 883-890 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hori, M.: "Mycalolide-B a novel and specific inhibitor of actomyosin ATPase isolated from marine sponge." FEBS Lett.322. 151-154 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Osada, H.: "Developments in industrial microbiology series (Wrn.C.Brown Publishers)" Microbial Metabolites. Vol.32. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] UBUKATA,M.,CHENG,X-C.,ISOBE,M. & ISONO,K.: "Absolute configuration of tautomycin,a protein phosphatase inhibitor from a streptomycete." J.Chem.Soc.Perkin Trans. 1. 617-623 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] KOBINATA,K.,KOSHINO,H.,KUDO,T.,ISONO,K. & OSADA,H: "RK-397,a new oxo pentaene antibiotic." J.Antibiotics. 46. 1616-1618 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] HOSOYA,N.,MITSUI,M.,TAZAWA,F.,ISHIHARA,H.,OZAKI,H.,KARAKI,M.,HARISHORNE,O.S & MOHRI,H: "Changes in the cytoskeletal structure of cultured smooth muscle cells induced by calyculin-A." J.Cell.Sci.105. 883-890 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] HORI,M.,SATO,S.,SHIN,YZ.,OZAKI,H.,FUSETANI,N.& KARAKI,H.: "Mycalolide-B,a novel and specific inhibitor of actomyosin ATPase isolated from marine sponge." FEBS Lett.322. 151-154 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] OSADA,H.& ISONO,K.: "Developments in industrial microbiology series,Microbial Metabolites.vol.32" Wm Brown Publishers, (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Usuki,T.,Obara,K.,Someya,T.,Ozaki,H.,Karaki H.,Fusteani,N.and Yabu,H.: "Calyculin A increases voltage-dependent inward current in smooth muscle cells isolated from guinea pig taenia coli." Experientia. 47. 939-941 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shibata,S.,Satake,N.,Morikawa,M.,Kown,S.,C.,Karaki,H.,kurahshi,K.,Sawacla.T.and Kodama.I.: "The in hibitory action of okadaic acid on mechanical responses in gumea-pig vas deferens." Eur.J.Pharmacol.193. 1-7 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 堀 正敏,唐木 英明: "化学と生物30巻3号" 東大出版会, 9 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 唐木 英明: "海洋資源と医薬品2" 広川書店, 11 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Hori,J.Magae,Y.-G.Han,D.J.Hartshorne and H.Karaki.: "A novel phosphatase inhibitor,tautomycin.Effect on smooth muscle." FEBS Lett.285. 145-148 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.G.Tansey,M.Hori,H.Karaki.K.E.Kamm.and J.T.Stull.: "Okadaic acid uncouples myosin light chain phosphorylation and tension in smooth muscle." FEBS Lett.270. 219-221 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 唐木 英明 (監)矢島 治明 (編)塩入 孝之、大泉 康: "新しいタンパク質脱リン酸化酵素阻害剤オカダ酸とカリクリンAの薬理作用 続医薬品の開発=海洋資源と医薬品II" 広川書店(東京), 10 (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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