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2001 Fiscal Year Final Research Report Summary

Studies on control mechanism of protein phosphatases ds a network system of information

Research Project

Project/Area Number 10480162
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

KIKUCHI Kunimi  Hokkaido Univ. Inst. Genet. Med. Prof., 遺伝子病制御研究所, 教授 (20006117)

Co-Investigator(Kenkyū-buntansha) TANUMA Nobuhiro  Hokkaido Univ. Inst. Genet. Med. Inst., 遺伝子病制御研究所, 助手 (40333645)
NAKAMURA Kouji  Hokkaido Univ. Inst. Genet. Med. Inst., 遺伝子病制御研究所, 助手 (70281839)
SHIMA Hiroshi  Hokkaido Univ. Inst. Genet. Med. Asso. Prof., 遺伝子病制御研究所, 助教授 (10196462)
Project Period (FY) 1998 – 2001
Keywordsprotein phosphatase / phosphotyrosine phosphatase / dual specificity phosphatase / PTPε / tautomycetin / cell differentiation / IL-6 / apoptosis
Research Abstract

Our results are summarized as follows:
1. Regulation of cytokine signaling by PTPεC
(1) PTPεC strongly suppressed IL-6-induced M1 differentiation in PTPεC activity-dependent manner. This suppression is due to suppression of JAK-activation.
(2) This suppression by PTPεC was observed in STAT-activation through IL6R and IL10R, but not in those via IFNα/βR and IFNγR.
2. Structure and function of a novel dual specificity phosphatase, MKP-7
(1) MKP-7 has Rhodariese domain, catalytic domain, NLS, and NES.
(2) Substrate specificity is in the order ot JNK>p38>>ERK.
(3) MKP-7 is a shuttle protein between cytosol and nucleus.
3. Structure and function of a novel PP1-inhibitor, 1-4
(1) 1-4 strongly inhibits PP1, IC_<50> being 0.2 nM.
(2) 1-4interacts with PP1C on at least three sites.
4. Structure-function relationship of tautomycin and its related compounds
(1) Different moieties of tautomycin are involved in protein phosphatase inhibition and induction of apoptosis.
(2) Tautomycetin is found to be a strong and specific inhibitor for PP1.

  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Noriko Urushibara: "The selective reduction in PTPδ expression in rat hepatomas"International Journal of Oncology. 12(3). 603-607 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeshi Kawamura: "Different moieties of tautomycin involved in protein phosphatase inhibition and induction of apoptosis"Biochemical Pharmacology. 55(7). 995-1003 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ken Nomoto: "Activation of protein phosphatase 1α promoter in ascites hepatoma cells"International Journal of Oncology. 13(2). 331-334 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nobuhiro Tanuma: "Distinct promoters control transmembrane and cytosolic protein tyrosine phosphatase epsilon expression during macrophage differentiation"European Journal of Biochemistry. 259(1-2). 46-54 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoko Imai: "Up-regulation of nuclear PP1α and PP1δ in hepatoma cells"International Journal of Oncology. 14(1). 121-126 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shu-ichi Matsuzawa: "Thyrsiferyl 23-acetate and its derivatives induce apoptosis in various T-and B-leukemia cells"Bioorganic & Medicinal Chemistry. 7(2). 381-387 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinya Mitsuhashi: "The spiroketals containing a benzyloxymethyl moiety at C8 position showed the most potent apoptosis-inducing activity"Bioorganic & Medicinal Chemistry Letter. 9(14). 2007-2012 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kunimi Kikuchi: "The apoptosis-inducing activity of the two protein phosphatase inhibitors, tautomycin and thyrsiferyl 23-acetate, is not due to the inhibition of protein Phosphatases PP1 and PP2A"International Journal of Molecular Medicine. 4(4). 395-401 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Koji Nakamura: "Molecular cloning and characterization of a novel dual-specificity protein phosphatase possibly involved in spermatogenesis"Biochemical Journal. 344(Pt3). 819-825 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kunimi Kikuchi: "Protein Phosphatases and Cancer"Current Topics in Biochemical Research. 1. 75-87 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinya Mitsuhashi: "Development of an assay method for activities of serine/threonine protein phosphatase type 2B (calcineurin) in crude extracts"Analytical Biochemistry. 278(2). 192-197 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sei-Eun Kim: "Increased expression of NIPP-1 mRNA positively correlated with malignant phenotype in rat hepatomas"International Journal of Oncology. 16(4). 751-755 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sei-Eun Kim: "Broad specificity in binding of NIPP-1, nuclear inhibitor of protein phosphtase-1, to PP1 isoforms in vivo"Tohoku Journal of Experimental Medicine. 191(1). 39-45 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motoi Kanagawa: "Membrane enzyme systems responsible for the Ca^<2+>-dependent phosphorylation of Ser^<27>, the independent phosphorylation of Tyr^<10> and Tyr^7, and the dephosphorylation o these phosphorylated residues in the α-chain of H/K-ATPase"Journal of Biochemistry. 127(5). 821-828 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nobuhiro Tanuma: "Protein tyrosine phosphatase, PTPεC, inhibits Jak-STAT signaling and differentiation induced by IL-6 and LIF in M1 leukemia cells"Journal of Biological Chemistry. 275(36). 28216-28221 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kouhei Masuda: "Expression and comparative chromosomal mapping of MKP-5 genes DUSP10/Dusp10"Cytogenetics and Cell Genetics. 90(1-2). 71-74 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Haruki Shirato: "Identification and characterization of a novel protein inhibitor of type-1 protein phosphatase"Biochemistry. 39(45). 13848-13855 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Haruki Shirato: "Expression in hepatomas and chromosomal localization of rat protein phosphatase 5 gene"International Journal of Oncology. 17(5). 909-912 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chikako Fukukawa: "Up-regulation of I-2^<PP2A>/SET gene expression in rat primary hepatomas and regenerating livers"Cancer Letters. 161(1). 89-95 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kunimi Kikuchi: "New apoptosis-inducing agents : Thyrsiferyl 23-acetate, tautomycin, and their related compounds"Drugs of the Future. 25(5). 501-507 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Bettina Linck: "Functional properties of the rat phosphatase 1α promoter"Molecular and Cellular Biochemistry. 223(1-2). 123-129 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinya Mitsuhashi: "Tautomycetin is a novel and specific inhibitor of serine/threonine protein phosphatase type 1, PP1"Biochemical and Biophysical Research Communications. 287(2). 328-331 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kouhei Masuda: "MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein"Journal of Biological Chemistry. 276(42). 39002-39011 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nobuhiro Tanuma: "Protein tyrosine phosphatase εC selectively inhibits interleukin-6-and interleukin-10-induced JAK-STAT signaling"Blood. 98(10). 3030-3034 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Noriko Urushibara: "The selective reduction in PTPδ expression in rat hepatomas"Intrernational Journal of Oncology. 12(3). 603-607 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeshi Kawamura: "Different moieties of tautomycin involved in protein phosphatase inhibition and induction of apoptosis"Biochemical Pharmacology. 55(7). 995-1003 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ken Nomoto: "Activation of protein phosphatase 1α promoter in ascites hepatoma cells"International journal of Oncology. 13(2). 331-334 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nobuhiro Tanuma: "Distinct promoters control transmembrane and cytosolic protein tyrosine phosphatase ε expression during macrophage differentiation"Eurpean Journal of Biochemistry. 259(1-2). 44-46 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoko Imai: "Up-regulation of nuclear PP1α and PP1δ in hepatoma cellsUp-regulation of nuclear PP1α and PP1δ in hepatoma cells"International Journal of Oncology. 14(1). 21-29 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shu-ichi Matsuzawa: "Thyrsiferyl 23-acetate and its derivatives induce apoptosis in various T- and B-leukemia cell"Bioorganic & Medicinal Chemistry. 7(2). 381-387 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinya Mitsuhashi: "The spiroketals containing a benzyloxymethyl moiety at C8 position showed the most potent apoptosis-inducing activity"Bioorganic & Medicinal Chemistry Letter. 9(14). 2007-2012 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kunimi Kikuchi: "The apoptosis-inducing activity of the two protein-phosphatase inhibitors, tautomycin and thyrsiferyl 23-acetate, is not due to the inhibition of protein phosphatases PP1 and PP2A"Internationl Journal of molecular Medicine. 4(4). 395-401 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koji Nakamura: "Molecular cloning and characterization of a novel dual-specificity protein phosphatase possibly involved in spermatogenesis"Biochemical Journal. 344(Pt3). 819-825 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kunimi Kikuchi: "Protein phosphatases and cancer"Current Topics in Biochemical Research. 1. 75-87 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinya Mitsuhashi: "Development of an assay method for activities of serine/thereonine protein phosphatase type 2B (calsuneurin) in crude extracts"Analytical Biochemistry. 278(2). 192-197 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sei-Eun Kim: "Increased expressioon of NIPP-1 mRNA positively correlated with malognant phenotype in rat hepatomas"International Journal of Oncology. 16(4). 751-755 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sei-Eun Kim: "Broad specifity in binding of NIPP-1, nuclear inhibitor of protein phosphatase-1, to PP1 isoforms in vivo"Tohoku Journal of Exprimental Medicine. 191(11). 39-45 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motoi Kanagawa: "Membrane enzyme systems responsible for the Ca^<2+>- dependent phosphorylation of Ser^<27>, the independent phosphorylation of Tyr^<10> and Tyr^7, and the dephosphorylation of these phosphorylated residues in the α-chain of H/K-ATPase"Journal of Biochemistry. 127(5). 821-828 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nobuhiro Tanuma: "Protein tyrosine phosphatase, PTPεC, inhibits Jak-STAT singnaling and differentiation induced by IL-6 and LIF in M1 leukemia cells"Journal of Biological Chemistry. 275(36). 28216-28221 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kouhei Masuda: "Expression and comparative charomosomal mapping of MKP-5 genes DUSP10-Dusp10"Cytogenetics and Cell Genetics. 90(1-2). 71-74 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Haruki Shirato: "Identification and characterization of a novel protein inhibitor of type-1 protein phosphatase"Biochemistry. 39(45). 13848-13855 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Haruki Shirato: "Expression in hepatomas and charomosomal localization of rat protein phosphatase 5 gene"International Journal of Oncology. 17(5). 909-912 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chikako Fukukawa: "Up-regulation of 1-2^<PP2A>-SET gene expression in rat primary hepatomas and regenerating levers"Cancer Letters. 161(1). 89-95 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kunimi Kikuchi: "New apotosis-inducing agents: thyrsifely 23-acetate, tautomycin, and their related compounds"Drugs of the Future. 25 (5). 501-507 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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