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The roles in neuronal differentiation of Ca^<2+>/calmodulin-dependent phosphorylation of microtubule proteins

Research Project

Project/Area Number 07680847
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKumamoto University

Principal Investigator

YAMAMOTO Hideyuki  Kumamoto University School of Medicine, Pharmacology, Assistant Professor, 医学部, 講師 (60191433)

Co-Investigator(Kenkyū-buntansha) FUKUNAGA Kohji  Kumamoto University School of Medicine, Pharmacology, Associate Professor, 医学部, 助教授 (90136721)
MIYAMOTO Eishichi  Kumamoto University School of Medicine, Pharmacology, Professor, 医学部, 教授 (50109659)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsAlzheimer's disease / Ca^<2+> / Calmodulin / Neuronal differentiation / CaM kinase II / Microtubule-associated protein 2 / PC12 cells / Antiphosphopeptide antibody / 細胞骨格蛋白質 / 蛋白質燐酸化酵素 / 分子生物学
Research Abstract

1) In order to investigate the physiological roles of Ca^<2+>/calmodulin-dependent protein kinase II (CaM kinase II) in neuronal differentiation, we transfected the cDNA of the alpha subunit of mouse CaM kinase II into PC12 cells. We have established the subclonal cell lines that constitutively express the transfected CaM kinase II.The phosphorylation of microtubule-associated protein 2 (MAP2) in these cell lines was higher than in the wild type cells, and was enhanced by treatment with ionomycin. 2) The two antiphosphopeptide antibodies to tau indicate that tau in the peripheral nervous system and Alzheimer's disease brain is highly phosphorylated at serine 199, serine 202 and serine 396.3) We synthesized a peptide (MAP2 peptide) which included serine 1562 of MAP2. MAP2 peptide was strongly phosphorylated by CaM kinase II.4) We prepared antiphosphopeptide antibody which reacted with MAP2 phosphorylated at serine 1562 by CaM kinase II.5) The phosphorylation of MAP2 in cerebellar culture cells was enhanced by treatment with ionomycin.
These results suggest that CaM kinase II regulates the functions of MAP2 in the cells and that phosphorylation of tau is increased in Alzheimer's disease brain. The antiphosphopeptide antibody to MAP2 is useful for the investigation of phosphorylation of MAP2 by CaM kinase II in the cells.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] T.Ono: "Dephosphorylation of abnormal sites of tau factor by protein phosphatases and its implication for Alzheimer's Disease" Neurochem.Int.26. 205-215 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamamoto: "Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) by proline-directed protein kinases and its dephosphorylation" J.Neurochem.65. 802-809 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.Sun: "Preparation of tau from the peripheral nerve : Presence of insoluble low molecular weight tau with high phosphorylation" Biochem.Biophys.Res.Commun.210. 338-344 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamamoto: "Dephosphorylation of fetal-tau and paired herical filaments-tau by protein phosphatases 1 and 2A and calcineurin" J.Biochem.118. 1224-1231 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.He: "Modification of neurofilament proteins by possible metabolites of allyl chloride in vitro" Drug and Chemical Toxicology. 18. 315-331 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tashima: "Overexpression of Ca^<2+>/calmodulin-dependent protein kinase II inhibits neurite outgrowth of PC12 Cells" J.Neurochem.66. 57-64 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takemi Kimura: "Sequential changes of tau-site-specific phosphorylation during development of paired herical filaments" Dementia. 7. 177-181 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ken Ikegami: "Immunohistochemical examination of phosphorylated tau in granulovacuolar degeneration granules" Psy.Clin.Neurosci.50. 137-140 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yasuharu Oishi: "The effects of 2,5-hexandione and acrylamide on myosin heavy chain isoforms of slow and fast skeletal muscles of the rat" Toxicol.Appl.Pahrmacol.139. 15-21 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Megumi Nagano: "Cross-linking of ovalbumin or neurofilament proteins by allyl chloride in vitro" J.Occup.Health. 38. 43-44 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Yanagihara: "Phosphorylation of chromogranin A and catecholamine secretion stimulated by elevation of intracellular Ca^<2+> in cultured bovine adrenal medullary cells" J.Biol.Chem.271. 17463-17468 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Seiji Hokimoto: "Expression of angiotensin-converting enzyme in remaining viable myocytes of human ventricles after myocardial infarction" Circulation. 94. 1513-1518 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Ono, H.Yamamoto, K.Tashima, H.Nakashima, E.Okumura, K.Yamada, S.Hisanaga, T.Kishimoto, T.Miyakawa and E.Miyamoto: "Dephosphorylation of abnormal sites of tau factor by protein phosphatases and its implication for Alzheimer's Disease." Neurochem.Int.26. 205-215 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamamoto, F.Arakane, T.Ono, K.Tashima, E.Okumura, K.Yamada, S.Hisanaga, K.Fukunaga, T.Kishimoto and E.Miyamoto: "Phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) by proline-directed protein kinases and its dephosphorylation." J.Neurochem.65. 802-809 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.Sun, Tashiro, S.Hirai, H.Yamamoto, E.Miyamoto and Y.Komiya: "Preparation of tau from the peripheral nerve : Presence of insoluble low molecular weight tau with high phosphorylation." Biochem.Biophys.Res.Commun.210. 338-344 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Yamamoto, M.Hasegawa, T.Ono, K.Tashima, Y.Ihara and E.Miyamoto: "Dephosphorylation of fetal-tau and paired helical filaments-tau by protein phosphatases 1 and 2A and calcineurin." J.Biochem.118. 1224-1231 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.He, M.Nagano, H.Yamamoto, E.Miyamoto and M.Futatsuka: "Modification of neurofilament proteins by possible metabolites of allyl chloride in vitro." Drug and Chemical Toxicol.18. 315-331 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Tashima, H.Yamamoto, C.Setoyama, T.Ono and E.Miyamoto: "Overexpression of Ca^<2+>/calmodulin-dependent protein kinase II inhibits neurite outgrowth of PC12 Cells." J.Neurochem.66. 57-64 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Kimura, T.Ono, J.Takamatsu, H.Yamamoto, K.Ikegami, A.Kondo, M.Hasegawa, Y.Ihara, E.Miyamoto and T.Miyakawa: "Sequential changes of tau-site-specific phosphorylation during development of paired helical filaments." Dementia. 7. 177-181 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Ikegami, T.Kimura, S.Katsuragi, T.Ono, H.Yamamoto, E.Miyamoto and T.Miyakawa: "Immunohistochemical examination of phosphorylated tau in granulovacuolar degeneration granules." Psy.Clin.Neurosci.50. 137-140 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Oishi, H.Yamamoto, M.Nagano, E.Miyamoto and M.Futatsuka: "The effects of 2,5-hexanedione and acrylamide on myosin heavy chain isoforms of slow and fast skeletal muscles of the rat." Toxicol.Appl.Pharmacol.139. 15-21 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Nagano, Y.He, H.Yamamoto, E.Miyamoto and M.Futatsuka: "Cross-linking of ovalbumin or neurofilament proteins by allyl chloride in vitro." J.Occup.Health. 38. 43-44 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Yanagihara, Y.Oishi, H.Yamamoto, M.Tsutsui, J.Kondoh, T.Sugiura, E.Miyamoto and F.Izumi: "Phosphorylation of chromogranin A and catecholamine secretion stimulated by elevation of intracellular Ca^<2+> in cultured bovine adrenal medullary cells." J.Biol.Chem.271. 17463-17468 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Hokimoto, H.Yasue, K.Fujimoto, H.Yamamoto, K.Nakao, K.Kaikita, R.Sakata and E.Miyamoto: "Expression of angiotensin-converting enzyme in remaining viable myocytes of human ventricles after myocardial infarction." Circulation. 94. 1513-1518 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takemi Kimura: "Sequential changes of tau-site-specific phosphorylation during development of paired helical filaments" Dementia. 7. 177-181 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ken Ikegami: "Immunohistochemical examination of phosphorylated tau in granulovacuolar degeneration granules" Psy.Clin.Neurosci.50. 137-140 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasuharu Oishi: "The effects of 2,5-hexandione and acrylamide on myosin heavy chain isoforms of slow and fast skeletal muscles of the rat" Toxicol.Appl.Pharmacol.139. 15-21 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Megumi Nagano: "Cross-linking of ovalbumin or neurofilament proteins by allyl chloride in vitro" J.Occup.Health. 38. 43-44 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] N.Yanagihara: "Phosphorylation of chromogranin A and catecholamine secretion stimulated by elevation of intracellular Ca^<2+> in cultured bovine adrenal medullary cells" J.Biol.Chem.271. 17463-17468 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Seiji Hokimoto: "Expression of angiotensin-converting enzyme in remaining viable myocytes of human ventricles after myocardial infarction" Circulation. 94. 1513-1518 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] X.Sun: "Preparation of tau from the periferal nerve : Presence of insoluble low molecular weight tau with high phosphorylation" Biochem.Biophys.Res.Commun.210. 338-344 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Yamamoto: "Dephosphorylation of fetal-tau and paired helical filaments-tau by protein phosphatases 1 and 2A,and calcineurin" J.Biochem.118. 1224-1231 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Y.He: "Modifications of neurofilament proteins by possible metabolites of allyl chloride in vitro" Drug and Chemical Toxicology. 18. 315-331 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Tashima: "Overexpression of Ca^<2+>/calmodulin-dependent protein kinase II inhibits neurite outgrowth of PC12 cells" J.Neurochem.66. 57-64 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 山本秀幸: "脳の細胞情報伝達機構に関する分子薬理学的研究" 日薬理誌. 107. 9-19 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 山本秀幸: "MAP1A,2[脳・神経タンパク質、接着タンパク質](廣川タンパク質化学 第9巻:野村靖幸編集)" 廣川書店, 5 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 山本秀幸: "タウタンパク質[脳・神経タンパク質、接着タンパク質](廣川タンパク質化学 第9巻:野村靖幸編集)" 廣川書店, 4 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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