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Genome pharmacology on novel calcium signaling in diseases

Research Project

Project/Area Number 10044267
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionMie University

Principal Investigator

TANAKA Toshio  Mie University, Faculty of Medicine, Professor, 医学部, 教授 (00135443)

Co-Investigator(Kenkyū-buntansha) NISHIMURA Yuhei  Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (30303720)
NAKA Michiko  Mie University, Faculty of Medicine, Assistant, 医学部, 助手 (10093139)
BERCHTOLD M.  コペンハーゲン大学, 理学部, 教授
HEIZMANN C.W  チューリッヒ大学, 医学部, 教授
林 正晃  三重大学, 医学部, 助手 (80291417)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 1999: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
KeywordsS100 Protein Family / S100C / Disease / Gene Expression / calcium / Actin Binding Proteins / カルシウム結合蛋白質 / 種々の病態
Research Abstract

Recently, we purified S100C, a novel CィイD12+ィエD1-binding protein and cloned and sequenced its cDNA. S100C is a novel member of S100 protein family, exhibiting several unique properties. S100 proteins became of major interest because of their close association with several human diseases and their use as prognostic indicators of different tumor types. S100C was found to be highly expressed in colorectal center, suggesting a role in cell transformation, in agreement with the localization of the S100C gene on human chromosome 1q21 a region most frequently amplified in tumor tissues. The purpose of this study was to investigate the differential expression of S100C in a number of human tissues and to determine the distinct intracellular localization of S100C by confocal laser scanning microscopy to obtain more information about S100 protein cell signaling. Moreover, we found that S100C interacts not only with annexins as previous reported, but also with actin in a CィイD12+ィエD1-dependent manner. In conclusion, (1) A single species of transcript of expected size (about 0.5 kb) was detected at high level in placenta. Intermediate levels were found in adult heart, adult and fatal lung and kidney, as well as adult pancreas. Low levels were detected in adult skeletalmuscle, as well as adult and fetal liver, S100C was barely detectable in fetal or adult brain. However, S100C is predominantly localized in the nucleus and less in the cytoplasm of tumor cells. (2) we found that S100C is abundant in smooth muscle and is a CィイD12+ィエD1-dependent actin binding protein. Further, S100C inhibits actin-activated myosin MィイD12+ィエD1-ATPase activity by binding to actin only in the presence on CaィイD12+ィエD1. Our results suggest that S100C is a CィイD12+ィエD1DA-dependent actin binding protein and is involved in the CィイD12+ィエD1DA-dependent regulation of action filaments.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] Xiao Qing Zhao: "Ca2+-dependent Inhibition of Actin-activated Myosin Atpase Activity by S100C(S100A11), A Novel Member of the S100 Protein Family"Biochem. Biophys. Res. Commun.. 267. 77-79 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroyasu Inada: "Human S100A11 Exhibits Differential Steady-State RNA Levels in Various Tissues and Distinct Subcellular Localization"Biochem. Biophys. Res. Commun.. 263. 135-138 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hidenori Suzuki: "Heme Oxygenase-1 Gene Induction as an Intrinsic Regulation against Delayed Cerebral Vasospasm in Rats"The Journal of Clinical Investigation. 104. 59-66 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masaaki Hayashi: "Molecular Cloning and Characterization of Human PDE8B, a Novel Thyrid-Specific Isozyme of 3', 5'-Cyclic Nucleotide Phosphodiesterase"Biochem. Biophys. Res. Commun.. 250. 751-756 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Da-Yu Tian: "Overexpression of caltractin gene in Tumor-Infiltrating Lymphocytes"International Journal of Oncology. 13. 1135-1140 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomoaki Nakamura: "A Unique Exon-intron Organization of a Porcine S100C Gene : Close Evolutionary Relationship to Calmodulin Genes"Biochem. Biophys. Res. Commun.. 243. 647-652 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Terumasa Mino: "Two distinct actin-binding sites of smooth muscle calponin"European Journal of Biochemistry. 251. 262-268 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Cornelia Franz: "Binding of Ca^<2+> and Zn^<2+> to Human Nuclear S100A2 and Mutant Proteins"The Journal of Biological Chemistry. 270 30. 18826-18834 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Thomas A. Millward: "Calcium regulation of Ndr protein kinase mediated by S100 calcium-binding proteins"The EMBO Journal. 17 20. 5913-5922 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 田中利男: "カルシウム結合蛋白質"日本臨床. 57. 275-278 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 西村有平: "遺伝子発現プロフィール解析とゲノム創薬科学"実験医学. 17 8. 980-984 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Xiao Qing Zhao: "CィイD12+ィエD1-dependent Inhibition of Actin-activated Myosin Atpase Activity by S100C (S100A11), A Novel Member of the S100 Protein Family"Biochem. Biophys. Res. Commun.. 267. 77-79 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroyasu Inada: "Human S100A11 Exhibits Differential Steady-State RNA Levels in Various Tissues and Distinct Subcellular Localization"Biochem. Biophys. Res. Commun.. 263. 135-138 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hidenori Suzuki: "Heme Oxygenase-1 Gene Induction as an Intrinsic Regulation against Delayed Cerebral vasospasm in Rats"The Journal of Clinical Investigation. 104. 59-66 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masaaki Hayashi: "Molecular Cloning and Characterization of Human PDE8B, a Novel Thyrid-Specific Isozyme of 3', 5'-Cyclic Nucleotide Phosphodiesterase"Biochem. Biophys. Res. Commun.. 250. 751-756 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Da-Yu Tian: "Overexpression of caltractin gene in Tumor-Infiltrating Lymphocytes"International Journal of Oncology. 13. 1135-1140 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomoaki Nakamura: "A Unique Exon-intron Organization of a Porcine S100C Gene : Close Evolutionary Relationship to Calmodulin Genes"Biochem. Biophys. Res. Commun.. 243. 647-652 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Terumasa Mino: "Two Distinct actin-binding sites of smooth muscle calponin"European Journal of Biochemistry. 251. 262-268 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Cornelia Farnz: "Binding of CaィイD12+ィエD1 and ZnィイD12+ィエD1 to Human Nuclear S100A2 and Mutant Proteins"The Journal of Biological Chemistry. 273 30. 18826-18834 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Thomas A. Millward: "Calcium regulation of Ndr protein kinase mediated by S100 calcium-binding proteins"The EMBO Journal. 17 20. 5913-5922 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kondo A: "Transcriptional and Posttranscriptional Regulation of Monocyte Chemoattractant Protein-3 Gene Expression in Human Endothelial Cells by Phorbol Ester and caMP Signaling"Immunology. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Zhao XQ: "Ca(2+)-dependent inhibition of actin-activated myosinATPase activity by S100C(S100A11), a novel member of the S100 protein family"Biochem Biophys Res Commun. 267・1. 77-79 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Suzuki H: "Heme oxygenase-1 gene induction as an intrinsicregulation against delayed cerebral vasospasm in rats"J Clin Invest. 104・1. 59-66 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuasa U: "Regulatory mechanisms of calponin phosphorylation inendothelin-1-induced contraction of porcine coronaryartery"J Mol Cell Cardiol. 31・6. 1281-1287 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inada H: "Human S100A11 exhibits differential steady-state RNAlevels in various tissues and a distinct subcellularlocalization"Biochem Biophys Res Commun. 263・1. 135-138 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishimura Y: "Molecular Cloning and Characterization of Mammalian Homologues of Vesicle-Associated Membrane Protein-Associated (VAMP-Associated) Proteins"Biochem Biophys Res Commun. 254・1. 21-26 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuhei Nishimura: "Molecular Cloning and Characterization of Mammalian Homologues of Vesicle-Associated Membrane Protein-Associated(VAMP-Associated)Proteins" Biochem.Biophys.Res.Commun.254. 21-26 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masaaki Hayashi: "Molecular Cloning and Characterization of Human PDE8B,a Novel Thyroid-Specific Isozyme of 3',5'Cyclic Nucleotide Phosphodiesterase" Biochem.Biophys.Res.Commun.250. 751-756 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Da-Yu Tian: "Overexpression of Caltractin Gene in Tumor-Infiltrating Lymphocytes" International Journal of Oncology. 13. 1135-1140 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomoaki Nakamura: "A unique exon-intron organization of a porcine S100C gene:close evolutionary relationship to calmodutin genes" Biochem.Biophys.Res.Commun.243. 647-652 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Terumasa Mino: "Two distinct actin-binding sites of smooth muscle calponin" European Journal of Biochemistry. 251. 262-268 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 鈴木秀謙: "RNAフィンガーブリンティング法を用いた脳血管攣縮関連遺伝子の探索研究" 脳血管攣縮. 13. 272-276 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Troxler,H.: "Electrospray Ionization Mass Spectrometry:Analysis of the Ca2+-Binding Properties of Human Recombinant alpha-Parvalbumin and Nine Mutant Proteins." Anal Biochem. 268・1. 64-71 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Camby,I.: "Supratentorial pilocytic astrocytomas,astrocytomas,anaplastic astrocytomas and glioblastomas are characterized by a differential expression of S100 proteins" Brain Pathol. 9・1. 1-19 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamashita,N.: "Distribution of a specific calcium-binding protein of the S100 protein family,S100A6(calcyclin),in subpopulations of neurons and glial cells of the adult rat nervous system" J Comp Neurol. 404・2. 235-257 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yang,Q.: "Demonstration of heterodimer formation between S100B and S100A6 in the yeast two-hybrid system and human melanoma" Exp Cell Res. 246・2. 501-509 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Van Ginkel,P.R.: "The identification and differential expression of calcium-binding proteins associated with ocular melanoma." Biochim Biophys Acta. 1448・2. 290-297 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fritz,G.: "spectroscopic investigations of its transition metal ion complexes,and three-Probing the structure of the human Ca2+- and Zn2+-binding protein S100A3:" Biochim Biophys Acta. 1448・2. 264-276 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ridinger,K.: "Clustered organization of S100 genes in human and mouse." Biochim Biophys Acta. 1448・2. 254-263 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mori,M.: "Immunohistochemical localization of S100A1 and S100A6 in postnatally developing salivary glands of rats." Histochem Cell Biol. 110・6. 579-587 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Millward,T.A.: "Calcium regulation of Ndr protein kinase mediated by S100 calcium-binding proteins." Embo J. 17・20. 5913-5922 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Franz,C.: "Binding of Ca2+ and Zn2+ to human nuclear S100A2 and mutant proteins." J Biol Chem. 273・30. 18826-18834 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mandinova,A.: "Distinct subcellular localization of calcium binding S100 proteins in human smooth muscle cells and their relocation in response to rises intracellular calcium." J Cell Sci. 111・pt 14. 2043-2054 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toida,K.: "Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb:III.Structural features of calbindin D28K-immunoreactive neurons." J Comp Neurol. 392・2. 179-198 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shrestha,P.: "Localization of Ca(2+)-binding S100 proteins in epithelial tumours of the skin." Virchows Arch. 432・1. 53-59 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Baldellon,C.: "15N NMR relaxation studies of calcium-loaded parvalbumin show tight dynamics compared to those of other EF-hand proteins." Biochemistry. 37・28. 9964-9975 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fischer,R.: "High affinity calmodulin target sequence in the signalling molecule PI 3-kinase." Febs Lett. 425・1. 175-177 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ye,Q.: "Corrigendum to: ‘Structure and expression of the chicken calmodulin I gene" Gene. 213・1-2. 225 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中利男: "21世紀の創薬科学(薬理ゲノム科学と創薬)" 共立出版, 18 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中利男: "よくわかるRDE3阻害薬の基礎と臨床(CAMPとPDE阻害薬の経緯およびPDEのアイソザイムとその分布)" Excerpta Medica, 11 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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