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Function of Calcium-Dependent Protease in Down Regulation of Protein Dinase C

Research Project

Project/Area Number 01480526
Research Category

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

Allocation TypeSingle-year Grants
Research Field 物質生物化学
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

SUZUKI Koichi  Tokyo Metropol. Inst. Med. Sci. Dept. Mol. Bio., Director, 遺伝情報部門, 部長 (80011948)

Co-Investigator(Kenkyū-buntansha) SAIDO Takaomi  Tokyo Metropol. Inst. Med. Sci. Dept. Mol. Bio., researcher, 遺伝情報部門, 研究員 (80205690)
OHNO Shigeo  Tokyo Metropol. Inst, Med. Sci. Dept. Mol. Bio., researcher, 遺伝情報部門, 研究所 (10142027)
AKITA Yoshiko  Tokyo Metropol. Inst. Med. Sci. Dept. Mol. Bio., researcher, 遺伝情報部門, 研究員 (40124432)
榎森 康文  東京都臨床医学総合研究部, 研究員 (60160389)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1990: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1989: ¥3,800,000 (Direct Cost: ¥3,800,000)
Keywordsprotein kinase C / calcium protease / phorbol ester / カルシウムイオン
Research Abstract

1. Phosphorylation of protein kinase C (PKC) is essential for its down-regulation
PKCalpha cDNA was expressed transiently in COS cells or stably in rat fibroblast 3Yl cells. The down regulation of PKCalpha was examined using these cells. A point mutation where Lys-368 at the putative ATP-binding site is replaced with arginine confers enhanced phorbol ester binding activity to both COS and 3Yl cells. Like endogenous and exogenously expressed wild type PKCalpha, the mutant is translocated from the cytosol to the particulate fraction when cells are treated with a phorbol ester (TPA). The mutant PKC is, however, not degraded after the TPA treatment, making a clear contrast to wild type PKC. The mutant is resistant to TPA-induced down-regulation. The mutant lacks kinase activity as expected, as judged by autophosphorylation and by a kinase assay. Autophosphorylation of PKC is a requisite for proteolytic cleavage associated with down-regulation of PKC.
2. Novel calcium independent protein kinase (nPKC) also transduce physiological signal
In GH4Cl cells, nPKCepsilon is expressed together with PKCalpha and beta II. nPKC epsilon is translocated to the cell membrane from the cytosol and down regulated when cells are treated with Thyrotropin Releasing Hormone (TRH), whereas other conventional PKC's are not down-regulated. Thus in GH4Cl cells, nPKCepsilon plays a crucial role distinct from that meadiated by calcium-dependent PKCalpha and beta II in cellular response elicited by both TRH and phorbol esters.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] S.Ohno,Y.Konno,Y.Akita,A.Yano,K.Suzuki: "A point mutation at the ATPーbinding site of protein kinase C alpha abolishes the kinase activity and renders it down regulation insensitive." J.Biol.Chem.265. 6296-6300 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] S.Ohno,S.Minoshima,S.Kudoh,J.Fukuyama,Y.Shimizu,S.ImajohーOhmi,N.Shimizu,K.Suzuki: "Four genes for the calpain family locate on four distinct human chromosomes" Cytogenet.Cell genet.53. 225-229 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] H.Sorimachi,S.Ohmi,Y.Emori,H.Kawasaki,T.Saido,S.Ohno,Y.: "A novel member of the calciumーdependent cysteine protease family.Minami,K.Suzuki" Biol.Chem.HoppeーSeyeler. 371. 171-176 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] K.Suzuki,S.Ohno: "Calcium activated neutral proteaseーーーstructural and functional implications." Cell Structure Function. 15. 1-6 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Y.Akita,S.Ohno,A.Yajima,K.Suzuki: "Possible role of calciumーindependent protein kinase C isozyme,nPKC epsilon in thyrotropin releasing hormone stimulated signal transduction" Biochem.Biophys.Res.Commun.172. 184-189 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] S.Osada,K.Mizuno,T.Saido,Y.Akita,K.Suzuki,T.Kuroki,S.Ohno: "A phorbol ester receptor/protein kinase C nPKC etha,a new family member of protein kinase C predominantly expressed in lung skin." J.Biol.Chem.265. 22434-22440 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohno, S.: "A point mutation at the ATP-binding site of protein kinase C alpha abolishes the kinase activity and renders it down regulation insensitive." J. Bio. Chem.265. 6296-6300 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ohno, S.: "Four genes for the calpain family locate on four distinct human chromosomes" Cytogenet. Cell Genet.53. 225-229 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Soromachi, H.: "A novel member of the calcium-dependent cysteine protease family." Bio. Chem. Hoppe-Seyler's. 371. 171-176 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Suzuki, K.: "calcium activated neutral protease ---Structural and functional implications" Cell Structure Function. 15. 1-6 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Akita, Y.: "Possible role of calcium-independent protein kinase C isozyme, nPKC epsilon in thyrotropin releasing hormone stimulated signal transduction." Bio chem. Biophys. Res. 172. 184-189 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Osada, S.: "A phorbol ester/receptor protein kinase C nPKC etha, a new family member of protein kinase C predominantly expressed in lung and skin." J. Bio. Chem.265. 22434-22440 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] S.Ohno,Y.Konno,Y.Akita,A.Yano,K.Suzuki: "A point mutation at the ATPーbinding site of protein kinase C alpha abolishes the kinase activity and renders it down regulation insensitive." J.Biol.Chem.265. 6296-6300 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Ohno,S.Minoshima,S.Kudoh,J.Fukuyama,Y.Shimizu,S.ImajohーOhmi,N.Shimizu,K.Suzuki: "Four genes for the calpain family locate on four distinct human chromosomes" Cytogenet.Cell Genet.53. 225-229 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] H.Sorimachi,S.Ohmi,Y.Emori,H.Kawasaki,T.Saido,S.Ohno,Y.: "A novel member of the calciumーdependent cysteine protease family.Minami,K.Suzuki" Biol.Chem.HoppeーSeyeler. 371. 171-176 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] K.Suzuki,S.Ohno: "Calcium activated neutral proteaseーーーstructural and functional implications." Cell Structure Function. 15. 1-6 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Y.Akita,S.Ohno,A.Yajima,K.Suzuki: "Possible role of calciumーindependent protein kinase C isozyme,nPKC epsilon in thyrotropin releasing hormone stimulated signal transduction" Biochem.Biophys.Res.Commun.172. 184-189 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Osada,K.Mizuno,T.Saido,Y.Akita,K.Suzuki,T.Kuroki S.Ohno: "A phorbol ester receptor/protein kinase C nPKC etha,a new family member of protein kinase C predominantly expressed in lung skin." J.Biol.Chem.265. 22434-22440 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Akiko Hata: "Tandemly reiterated negative and positive enhancer elements regulate transcription of a human gene for the large subunit of calcium-dependent protease" J.Biol.Chem.264. 6404-6411 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Akiko Hata: "Derect evidence that the kinase activity of protein kinase C is involved in transcriptional activation through a TPA-responsive element." FEBS Letters. 252. 144-146 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Hitoshi Wada: "Cell-type specific expression of the genes for the protein kinase C family:Down regulation of mRNAs for PKC alpha and nPKC epcilon upon invitro differenciation of a mouse neuroblastoma cell line 2a" Biochem.Biophys.Res.Commun.165. 533-538 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Yoshiko Akita: "Expression and properties of two distinct classes of the phorbol ester receptor family,four conventional PKCs and a novel protein kinase C." J.Biol.Chem.265. 354-362 (1990)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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