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Roles of proteases in signal transduction and their disorders

Research Project

Project/Area Number 03304029
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionNagoys City Unversity Medcal School

Principal Investigator

SASAKI Makoto  Nagoya City University Medical School, professor, 医学部, 教授 (10080003)

Co-Investigator(Kenkyū-buntansha) OHKUBO Iwao  Shiga University of Medical Science, Professor, 教授 (80152073)
高橋 健治  東京大学, 理学部, 教授 (70011533)
IWANAGA Sadaaki  Kyushu University, Faculty of Science, Professor, 理学部, 教授 (90029942)
SUZUKI Koichi  The University of Tokyo, Institute of Molecular and Cellular Biosciences, Profes, 分子細胞生物学研究所, 教授 (80011948)
KATUNUMA Nobuhiko  Tokushima Bunri University. Instituta for Heslth Sciences. Professor, 健康科学研究センター, 教授 (50035375)
木南 英紀  順天堂大学, 医学部, 教授 (10035496)
市原 明  徳島大学, 酵素科学研究所, 教授 (40035374)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥18,900,000 (Direct Cost: ¥18,900,000)
Fiscal Year 1993: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1992: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1991: ¥8,500,000 (Direct Cost: ¥8,500,000)
KeywordsLimited proteolysis / 94K calpain / Thrombomodulin / Hematocyte coagulation factor / Calpain activation due to inafarotion / Amyloidogenic protease / Intracellular protease transport / Antigen presentation / 筋組織特異的94Kカルバイン / カテプシン-インバリアント鎖による抗原提示の調節 / 筋組織特異的カルパイン / プロガストリンの活性化 / 心筋梗塞巣活性化カルパイン / カテプシンBの抗原阻囎への関与 / トランスゴルジ膜結合性プロセシングプロテアーゼ / プロテア-ゼによる情報発現 / プレプロタキキニン遺伝子発現調節因子 / カルパインの活性化 / カルパインペプチドの白血球遊走活性 / T細胞エイズレセプタ- / 26Sプロテアソ-ム / ニュ-カッスル病ウイルス
Research Abstract

This grant has facilitated the study of "Role of proteases in signal transductin and their disorders" during the last 3 years. The study was carried out under the following 4 categories.
1. Gene expression and regulation of the proteasse and the related bioactive substances.
2. Processing and transport of the precurcer proteins of the proteases and their inhibitors.
3. Induction and modulstion of signals by proteases, and the interaction of protains by the aid of proteases.
4. New functions of proteases
1. Regulatory factors for gene exprssion of preproteachykinin, a precurcer protein of substance P and substance K.were found to be 43kD and attach to DNA thrugh ths lsucine zipper domsin of the molecules. With respect to calpains. in addition to the m- and mu-calpains. novel calpain genes were found to be expressed linited in skeletal and smooth muscles. The former calpain contained 94kD large subunit and the latter two types of large subunits ; type 1 which contains calmodulin domain and ty … More pe 2 without calmodulin domain.
2. Proenzymes in the rat liver were fund to be Ca^<2+>-dependently activated in the tranagogi by the membrane-bound processingprotease. Progastrin secreted from the stomsch was also shown to be activated Ca^<2+>-dependently by the endopeptidase which recognizes dibasic amino acid sequence in the C-terminus of the molecule. Coagulation system of horseshoe crab was found to reside in the hemotocytes. Factor B, factor C, agglutinin and coagulation enzyme released from large granules and tackypressin from small granules were elucidated to form the cascade reaction system. Calpain, containing 94kD large subunit found in the nucleus was interpreted to be due to the transmembrane signal peptde in the large subunit.
3. A satisfactory condition for the activation of calpain wes demonstrated to be the N-terminus cleavage of the large subunit, and ths subsequently released N-terminal peptides from the large and small subunits ware found to be chemotactic for neutrophils, monocytes and T and B lymphocytes The interaction of HIV and helper T lymphocyte was shown to be organized between the virus envglope glycoprotein pg120 and the T lymphocyte trptase and CD4 on the cell surtace.
4. Multicatalytic high molecular weight proteass (proteasome) was shown to gain the special abllity to digest ubiquitinated protein through transformation of 20s complex to 28s in the presence of ATP.In the immunological event of antigen presentation by MHC class II, cathepsin B was sohwn to paly a crucial role in the prearation of the epitope peptides. Less

Report

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

    (45 results)

All Other

All Publications (45 results)

  • [Publications] Matsunaga Y.,Saibara T.,Kido H.and Katunuma N.: "Participation of cathepsin B in processing of antigen presentation to MHC class II" FEBS Letters. 324. 325-330 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sorimachi H.,Ishiura S.and Suzuki K.: "A novel tissue-specific calpain species expressed predominantly in the stomach comprises two alternative splicing products with and without Ca^<2+>-binding domain" J.Biol.Chem.268. 19476-19482 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Muta T.,Oda T.and Iwanaga S.: "Horseshoe crab coagulation factor B.A unique serine protease zymogen" J.Biol.Chem.268. 21384-21388 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchino T.,Sakurai Y.,Nishigai M.,Takahashi T.,Arakawa H.,Ikai A.and Takahashi K.: "Isolation and characterization of a novel serine proteinase complexed with α_2-macroglobulin from porcine gastric mucosa" J.Biol.Chem.268. 527-533 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ueyama H.,Han-Xiang D.and Ohkubo I.: "Molecular cloning and chromosomal assignment of the gene for human Zn-α_2-glycoprotein" Biochemistry. 32. 12968-12972 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tazawa R.,Hirosawa S.,Suzuki K.,Hirokawa K.and Aoki N.: "Functional characterization of the 5'-regulatory region of the human thrombomodulin gnen" J.Biochem.113. 600-603 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 早石 修 監修 小川 龍、佐々木 實 編集: "プロテアーゼとそのインヒビター-生理的意義および病態との関連" Medical View社, 362 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Katunuma N.,Suzuki K.,Travis J.and Fritz H.ed.: "Biological Functions of Proteases and Inhibitors" Japan Scientific Societies Press, 274 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ikei.A., Nishigai M., Tanaka K.and Ichihara A.: "Electron microscopy of 26 S complex containing 20 S proteasome" FEBS Letters. 292. 21-24 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ueno T., Muno D.and Kominami E.: "Membrane markers of endoplastic reticulum preserved in autophagic vacuolar membranes isolated from leupetin-administered rat liver" J.Biol.Chem.266. 18995-1899 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sasaki M., Kunimatsu M., Tada T., Nishimura J., Ma X.J.and Ohkubo I.: "Calpain and kininogen mediated inflammation" Biomed.Biochim.Acte.50. 499-508 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakaguchi T., Matsuda Y., Kiyokage R., Kawahara N., Kiyotani K., katunuma N., Nagai Y.and Yoshida T.: "Identification of endoprotease activity in the trans Golgi membranes of rat liver cells that specifically processes in vitro the fuslon glycprotain precurcor of virulent Newcastle disease virus" Virology.184. 504-512 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hirokawa K.and Aoki N.: "Up-regulation of thrombomodulin by activatin of hietalne H_1-receptors in human unbilical-vein endothelial cells in vitro" Biochem.J.276. 739-743 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishimura Y.and Kato K.: "Expression of mouse cathepain L cDNA in saccharomyces cerevisiae : Evidence that cathepsin L is sorted for targeting to yeast vacuole" Arch.Biochem.Biophys. 298. 318-324 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsunaga Y., Saibara T., Kido H.and katunuma N.: "Participation of cathepsin B in processing of antigen presentation to MHC class II" FEBS Letters. 324. 325-330 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sorimachi H., Ishiura S.and Suzuki K.: "A novel tissuespacific calpain spacise expressed predominatly in the stomach comprises two alternative splicing products with and without Ca^<2+>-binding domain" J.Biol.Cham.268. 19476-19482 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Muts T., Ode T, and Iwanaga S.: "Horseshoe crab coagulation factor B.A unique serine protease zymogen" J.Biol.Chem.268. 21384-21388 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchino T., Sakurai Y., Nishigai M., Takahashi T., Arakawa H., Ikai A.and Takahashi K.: "Isoiation and characterization of a novel serine proteinase comlexed with alpha_2-macroglobulin from porcine gastric mucosa" J.Biol.Chem.268. 527-533 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ueyama H., Han-Xiang D.and Ohkubo I.: "Molecular cloning and chromosomal assignmnet of the gene for human Zu-alpha_2-glycoprotein" Biochemistry. 32. 12968-12972 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tazawa R., Hirosawa, S., Suzuki K., Hirokawa K.and Aoki N.: "Functional characterlzation of the 5'-regulatiory region of the human thrombomobulin gene" J.Biochem.113. 600-603 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fukushima D., Konishi M., Maruyama R., Miyamoto, T., Ishiura S.and Suzuki K.: "Actvation of the aecretory pathway leads to a decrease in the intracellular anyloidogenic fragments generated from the amyloid protain precursor" Biochem.Biophys.Res.Commun.194. 202-207 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsunaga Y.,Saibara T.,Kido H.and Katunuma N.: "Participation of cathepsin B in processing of antigen presentation to MHC class II" FEBS Letters. 324. 325-330 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sorimachi H.,Ishiura S.and Suzuki K.: "A novel tissue-speciffic calpain species expressed predominantly in the stomach comprises two alternative splicing products with and without Ca^<2+>-binding domain" J.Biol.Chem.268. 19476-19482 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Muta T.,Oda T.and Iwanaga S.: "Horseshoe crab coagulation factor B. A unique serine protease zymogen" J.Biol.Chem.268. 21384-21388 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Uchino T.,Sakurai Y.,Nishigai M.,Takahashi T.,Arakawa H.,Ikai A.and Takahashi K.: "Isolation and characterization of a novel serine proteinase complexed with alpha_2-macroglobulin from porcine gastric mucosa" J.Biol.Chem.268. 527-533 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ueyama H.,Han-Xiang D.and Ohkubo I.: "Molecular cloning and chromosomal assignment of the gene for human Zn-alpha_2-glycoprotein" Biochemistry. 32. 12968-12972 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tazawa R.,Hirosawa S.,Suzuki K.,Hirokawa K.and Aoki N.: "Functional characterization of the 5′-regulatory region of the human thrombomodulin gene" J.Biochem.113. 600-603 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 早石 修監修 小川 龍、佐々木實編集: "プロテアーゼとそのインヒビター -生理的意義および病態の関連" Medical View 社, 362 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Katunuma N.,Suzuki K.,Travis J.and Fritz H.ed.: "Biological Functions of Proteases and Inhibitors" Japan Scientific Societies Press, 274 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Saido T.C,Shibata M.,Takenawa T.,Murofushi H.and Suzuki K.: "Positive regulation of μ-calpain action by polyphosphpinositides" J.Biol.Chem.267. 24585-24590 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shigematsu Y.,Miyata T.,Higashi s.,Miki T.Sadler J.E.and Iwanaga S.: "Expression of human soluble tissue factor in yeast and enzymatic properties of its complex with factor VIIa" J.Biol.Chem.267. 21329-21337 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kageyama T.,Ichinose M.Tsukada S.,Miki K.,Kurokawa K.,Koiwai O.,Tanji M.,Yakabe E.,: "Gastric prpcathepsin E and progastricsin from guinea pig" Athauda S.B.P.and Takahashi K.J.Biol.Chim.267. 16450-16459 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nishimura Y.and Kato K.: "Expression of mouse cathepsin L cDNA in saccharomyces cerevisiae:Evidence that cathepsin L is sorted for targetin to yeast vacuole" Arch.Biochem.Biophys.298. 318-324 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kominami E.,Ishido K.,Muno D.and Sato N.: "The Primary structure and tissus distribution of cathepsin C" Biol.Chem.Hoppe-Seyler. 373. 367-373 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Walker J.A.,Sakaguchi T.,Matsuda Y.,Yoshida T.and Kawaoka Y.: "Location and charactre of the cellular enzyme that cleaves the hemagglutinin of a virulent ayian influenza virus" Virology. 190. 278-287 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 鈴木 紘一(分担執筆): "食品の生体調節機能" 学会出版センター, 11 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 西村 行生,加茂 敬太郎(分担執筆): "日本生化学会編、新生化学実験講座 第一巻 タンパク質VI 合成および発現" 東京化学同人, 11 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sasaki M.,Kunimatsu M.,Tada T.,Nishimura J.,Ma X.J.and Ohkubo I.: "Calpain and kininogen mediated inflammation" Biomed.Biochim.Acta. 50(4ー6). 499-508 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kido H.,Fukutomi A.,and Katunuma N.: "Tryptase TL_2 in the membrane of human T4^+ lymphocytes is a novel binding protein of the V3 domain of HIVー1 envelope glycoprotein gp120" FEBS Letters. 286(1/2). 233-236 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ueno T.,Muno O.and Kominami E.: "Membrane markers of endoplasmic reticulum preserved in autophagic vacuolar membranes isolated from leupetinーadministered rat liver" J.Biol.Chem.266(28). 18995-18999 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ikai A.,Nishigai M.,Tanaka K.and Ichihara A.: "Electron microscopy of 26 S complex containing 20 S proteasome" FEBS Letters. 292(1/2). 21-24 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Muta T.,Miyata T.,Misumi K.,Tokunaga F.,Nakamura T.,Toh Y.and Iwanaga s.: "Limulus factor C:An endotoxinーsensitive serine protease zymogen with a mosaic structure of complementーlike,epidermal growth factorーlike and lectinーlike domains" J.Biol.Chem.266(10). 6554-6561 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Athauda S.B.P.,Takahashi T.,Inoue H.,Ichinose M.and Takahashi K.: "Proteolytic activity and cleavage specificity of cathepsin E at the physiological pH as examined towards the B chain of oxidized insulin" FEBS Letters. 292(1/2). 53-56 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 宮田 敏行,岩永 貞昭 (分担執筆): "注目の臨床実験検査法ー凝固因子の分子異常症の検出ー" 中山書店, 13 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 勝沼 信彦: "細胞内タンパク質分解ー機構・調節・病態ー" 東京化学同人, 131 (1992)

    • Related Report
      1991 Annual Research Report

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

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