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Regulation of ion channels by GTP-binding Proteins

Research Project

Project/Area Number 05044153
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionUniversity of Tokyo

Principal Investigator

KATADA Toshiaki  University of Tokyo, Faculty of Phamaceutical Sciences, 薬学部, 教授 (10088859)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Yoshihiro  Columbia University, Department of Pharmacology, 医学部・薬理学科, 助教授
KURACHI Yoshihisa  Osaka University, Faculty of Medicine, 医学部, 教授 (30142011)
HOSHINO Shin-ichi  University of Tokyo, Faculty of Pharmaceutical Sciences, 薬学部, 助手 (40219168)
HAZEKI Osamu  University of Tokyo, Faculty of Pharmaceutical Sciences, 薬学部, 助手 (80142751)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1994: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1993: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsGTP-binding proteins / Membrane receptors / Ion channels / Adenylyl cyclase / Signal transduction / ADP-ribosylation
Research Abstract

GTP-binding protein (G proteins) consisting of alpha, beta, gamma subunits, carry signals from agonist-bound receptors to effectors such as enzymes or ion channels. Since the functions of G proteins as the signal transducers are profoundly affected by cholera or pertussis toxin which transfers the ADP-ribosyl moiety of NAD^+ to the alpha subunits of G proteins, the toxin-catalyzed ADP-ribosylation has widely been used as a tool to study the roles of G proteins in signal transduction processes. In the present studies, we investigated mechanisms by which the activities of an inwardly rectifying K^+ channel and adenylyl cyclase are regulated by the subunits of G proteins.
1) Activation of inwardly rectifying K^+ channels by the betagamma subunits of G proteins. An inwardly rectifying K^+ channel in guinea pig cardiac atrial cells is activated by the stimulation of muscarinic cholinergic or A^1-purinergic receptors in a manner sensitive to pertussis toxin. In inside-out patches of the cell … More membranes, the betagamma subunits of G proteins activated the K^+ channels. Properties of the betagamma-induced activation of the K^+ channel appeared to be the same as those observed in GTP-dependent receptor-mediated activation of the K^+ channel. Moreover, the receptor-mediated activation of the K^+ channel was selectively inhibited by GDP-bound from of G_t (transducin). These results indicate that activation of inwardly rectifying K^+ channel coupling to membrane-bound receptors is mediated through the action] of betagammasubunits resolved from alphabetagammatrimer.
2) Activation of adenylyl cyclase by protein kinase C.Cyclic AMP formation within cells is altered upon the activation of protein kinase C.However, the site (s) to be modified by the kinase in the cyclic AMP formation pathway remains unclear. Thus, effects of protein kinase C on the activity of adenylyl cyclase were investigated with purified proteins. Protein kinase C could phosphorylate adenylyl cyclase type V directly, leading to a 20-fold increase in its catalytic activity. This activation was much larger than that stimulated by forskolin (5 fold). When forskolin and the protein phosphorylation were combined, the type 5 cyclase activity was increased more than 100 fold over the basal. Thus, it appears that protein kinase C directly and potently activates adenylyl cyclase. Less

Report

(2 results)
  • 1994 Final Research Report Summary
  • 1993 Annual Research Report

Research Products

(23 results)

All Other

All Publications (23 results)

  • [Publications] Mitsuhiko Yamada: "G_k and brain G_<βγ> activate muscarinic K^+ channel through the same mechanism" Journal of Biological Chemistry. 268. 24551-24554 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kenji Kontani: "NDA glycohydrolase specifically induced by retinoic acid in human leukemic HL-60 cells:Identification of the NAD glycohydrolase as CD38" Journal of Biological Chemistry. 268. 16895-16898 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.Terzic,et al.: "G proteins activate ATP-sensitive K^+ channels by antagonizing ATP-dependent gating" Neuron. 12. 885-893 (194)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Kawabe,et al.: "Differential activation of adenylyl cyclase by protein kinase C isoenzymes." Journal of Biological Chemistry. 269. 16554-16558 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuhiko Yamada,et al.: "Muscarinic K^+ channels are activated by betagamma subunits and inhibited by the GDP-bound form of alpha subunit of transducin." Biochem.Biophys.Res.Commun.200. 1484-1490 (2994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toshiaki.Katada,et al.: "Methods in Enzymology Vol.237(Heterotrimeric G Proteins;Purification and separation of closely related members of pertussis toxin-substrate G proteins)" Academic Press Inc., 561 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuhiko Yamada,et al.: "Methods in Enzymology Vol.238(Heterotrimeric G protein Effectors;Regulation of potassium channels by G-protein subunits and arachidonic acid metabolites)" Academic Press Inc., 561 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuhiro Yamada, et al.: "G_k and brain G_<betagamma> activate muscarinic K^+ channel through the same mechanism." Journal of Biological Chemistry. 268. 24551-24554 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Kontani, et al.: "NAD glycohydrolase specifically induced by retinoic acid in human leukemic HL-60 cells." Journal of Biological Chemistry. 268. 16895-16898 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] A.Terzic, et al.: "G proteins activate ATP-sensitive K^+ channels by antagonizing ATP-dependent gating" Neuron. 12. 885-893 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] J.Kawabe, et al.: "Differential activation of adenylyl cyclase by protein kinase C isoenzymes." Journal of Biological Chemistry. 269. 16554-16558 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuhiko Yamada, et al.: "Muscarinic K^+ channels are activated by betagamma subunits and inhibited by the GDP-bound form of alpha subunit of transducin." Bichem.Biophys.Res.Commun.200. 1484-1490 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toshiaki.Katada, et al.: Academic Press Inc.Methods in Enzymology Vol.237 (Heterotrimeric G Proteins ; Purification and separation of closely related members of pertussis toxin-substrate G proteins), 561 (131-139) (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuhiko Yamada, et al.: Academic Press Inc.Methods in Enzymology Vol.238 (Heterotrimeric G protein Effectors ; Regulation of potassium channels by G-protein subunits and arachidonic acid metabolites), 561 (394-422) (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mitsuhiko Yamada: "G_k and brain G_<βγ> activate muscarinic K^+ channel through the same mechanism" Journal of Biological Chemistry. 268. 24551-24554 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kenji Kontani: "NAD glycohydrolase specifically induced by retinoic acid in human leukemic HL-60 cells:Identification of the NAD glycohydrolase as CD38" Journal of Biological Chemistry. 268. 16895-16898 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshinori Takei: "Opposite coupling of prostaglandin E receptor EP_<3C> with G_s and G_o.Stimulation of G_s and inhibition of G_o" Journal of Biological Chemistry. 268. 26067-26070 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kazuyoshi Chiba: "Induction of starfish oocyte maturation by the βγ subunit of starfish G protein and possible existence of the subsequent effectors in cytoplasm" Molecular Biology of the Cell. 4. 1027-1034 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Astushi Inanobe: "Association of the βγ subunits of trimeric GTP-binding proteins with heat shock protein,hsp90" Journal of Biochemistry. 115 (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yoshinori Takei: "Possible involvement of a pertussis toxin-sensitive GTP-binding protein in protein transport into nuclei isolated from rat liver" Journal of Biochemistry. 115 (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 仁科博史: "Annual Review細胞生物学1993" 中外医学社, 349 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 堅田利明: "生体における情報伝達" 南江堂, 322 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 堅田利明: "レセプター-基礎と臨床-" 朝倉書店, 944 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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