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2001 Fiscal Year Final Research Report Summary

Studies on Ras signal transduction pathways

Research Project

Project/Area Number 12480209
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Molecular biology
Research InstitutionNatiomal Institute for Basic Biology (2001)
The University of Tokyo (2000)

Principal Investigator

KATSUKI Motoya  Natiomal Institute for Basic Biology, Director in General, 基礎生物学研究所, 所長 (20051732)

Project Period (FY) 2000 – 2001
Keywordssmall G protein / H-Ras / N-Ras / K-Ras / Signal Transduction / Long Term Potentiation / Hippocampus / knockout mice
Research Abstract

Glutamate receptors that are major excitatory neurotransmitter receptors in the central nervous system (CNS) lead to neuronal cell death when they are overactivated. Therefore, there may be some mechanisms that make a balance between excitotoxic and surviving signals when the receptors are normally activated. We have found that the H-Ras proteins are involved in the NMDA receptor tyrosine phosphorylation and suppress the Long-Term potentiation of the CAl region of the mouse hippocampus. We also found that NMDA stimulation, which conveys Ca^<2+> in-flux into the cell through the NMDA receptor channel, dramatically decreases tyrosine phosphorylation of NR2B subunit of the receptor in hippocampal slices as well as hippocampal cultured cells. This NMDA signaling is mediated by NR2B subunit because blockade of NR2B by a specific antagonist eliminates activation of the ERK and p38 MAPK activation and tyrosine dephosphorylation of NR2B and gene disruption of NR2B eliminates ERK activation by NMDA stimulation. Therefore, NR2B subunit of NMDA receptor regulates ERK pathway, p38 MAPK pathway and own phosphorylation upon NMDA stimulation to modulate a balance between excitotoxic and surviving signals.

  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] Kim, JM. te al.: "Inactivation of Cdc7 kinase in mouse ES cells results in S phase arrest and p53-dependent cell death"EMBO J. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsui, T. et al.: "K-Ras mediates cytokine-induced formation of E-cadherin-based adherens junctions during liver development"EMBO J. 21. 1021-1030 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hasegawa, S. et al.: "Apoptosis in neural crest cells by functional loss of APC tumor suppressor gene"Proc Natl Acad Sci U S A. 99. 297-302 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hisakawa, H. et al.: "Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) stimulates primitive and definitive erythropoiesis in mouse embryos expressing hGM-CSF receptors but not erythropoietin receptors"Blood. 98. 3618-3625 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishinakamura, R. et al.: "Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development"Development. 128. 3105-3115 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniguchi, S. et al.: "Structural fragility of blood vessels and peritoneum in calponin h1-deficient mice resulting in an increase in hematogenous metastasis and peritoneal dissemination of malignant tumor cells"Cancer Res. 61. 7627-7634 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kishimoto, Y. et al.: "Impaired delay but normal trace eyeblink conditioning in PLCbeta4 mutant mice"Neuroreport. 12. 2919-2922 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuzuki, T. et al.: "Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase"Proc Nati Acad Sci U S A. 98. 11456-11461 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirono, M. et al.: "Phospholipase Cbeta4 and protein kinase Caipha and/or protein kinase CbetaI are involved in the induction of long term depression in cerebellar Purkinje cells"J Biol Chem. 276. 45236-45242 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukami, K. et al.: "Requirement of phospholipase Cdelta4 for the zona pellucida-induced acrosome reaction"Science. 292. 920-923 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Moon, BG. et al.: "Functional dissection of the cytoplasmic subregions of the interleukin-5 receptor alpha chain in growth and immunoglobulin G1 switch recombination of B cells"Immunology. 102. 289-300 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kajiwara, K. et al.: "Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis"Genes Cells. 6. 99-106 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chusho, H. et al.: "Dwarfism and early death in mice lacking C-type natnuretic peptide"Proc Natl Acad Sci U S A. 98. 4016-4021 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshimoto, R. et al.: "Ca2+-Sensitization of contraction in the h1 calponin-deficient smooth muscle"Jpn J Pharmacol. 84. 474-475 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi, K. et al.: "Regulation of shortening velocity by calponin in intact contracting smooth muscles"Biochem Biophys Res Commun. 279. 150-157 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukui, T. et al.: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact"Proc Nati Acad Sci U S A. 97. 13760-13765 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato, M. et al.: "Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IEN-alpha/beta gene induction"Immunity. 13. 539-548 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ise, k.et al.: "Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis"Oncogene. 19. 2951-2956 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ichise, T. et al.: "mGluR1 in cerebellar Purkinje cells essential for long-term depression, synapse elimination, and motor coordination"Science. 288. 1832-1835 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murai, H. et al.: "Studies of in vivo mutations in rpsL transgene in UVB-irradiated epidermis of XPA-deficient mice"Mutat Res. 450. 181-192 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shioyama, Y. et al.: "Different mutation frequencies and spectra among organs by N-methyl-N-nitrosourea in rpsL (strA) transgenic mice"Jpn J Cancer Res. 91. 482-491 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda, M. et al.: "PLC beta 4-independent Ca2+ rise via muscarinic receptors in the mouse suprachiasmatic nucleus"Neuroreport. 11. 907-912 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura, N. et al.: "Cardiac fibrosis in mice lacking brain natriuretic peptide"Proc Nati Acad Sci U S A. 97. 4239-4244 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Manabe, T. et al.: "Regulation of long-term potentiation by H-Ras through NMDA receptor hosphorylation"J Neurosci. 20. 2504-2511 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sunahara, s. et al.: "The oocyte-specific methylated region of the U2afbp-rs/U2af1-rs1 gene is dispensable for its imprinted methylation"Biochem Biophys Res Commun. 268. 590-595 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kim, JM. et al: "lnactivation of Cdc7 kinase in mouse ES cells results in S phase arrest and p53-dependent cell death"EMBO J. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsui. T. et al: "k-Ras mediates cytokine-induced formation of E-cadherin-based adherens junctions during liver development"EMBO J. 21. 1021-1030 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hasegawa.S. et al: "Xpoptosis in neural crest cells by functional loss of ARC tumor suppressor gene."Proc Natl Acad Sci USA. 99. 297-302 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hisakawa.H., et al: "Human granulocyte-macrophage colony-stimulating factor (hGM-CSR stimulates orimitivft and definitive erythropoiesis in mouse embryos expressing hGM-CSF receptors but not erythropoietin receptors."Blood. 98. 3618-3625 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishinakamura,R. et al: "Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development."Development. 128. 3105-3115 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniguchi.S. et al: "Structural fragility of blood vessels and peritoneum in calponin hi-deficient mice resulting in an increase in hematogenous metastasis and peritoneal dissemination of malignant tumor cells"Cancer Res. 61. 7627-7634 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kishimoto.Y. et al: "lmpaired delay but normal trace eyeblink conditioning in PLCbeta4 mutant mice."Neuroreport. 12. 2919-2922 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuzuki.T. et al: "Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase."Proc Natl Acad Sci USA. 98. 11456-11641 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirono,M. et al: "Phospholipase Cbeta4 and protein kinase Calpha and/or protein kinase Cbetal are involved in the induction of long term depression in cerebellar Purkinje cells."J Biol Chem. 276. 45236-45242 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukami.K. et al: "Requirement of phospholipase Cdelta4 for the zona pellucida-induced acrosome reaction."Science. 292. 920-923 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Moon.BG. et al: "Functional dissection of the cytoplasmic subregions of the interleukin-5 receptor alpha chain in growth and immunoglobulin G1 switch recombination of B cells."Immunology. 102. 289-300 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kajiwara.K. et al: "Sez4 gene encoding an elongation subunit of DNA polymerase zeta is required for normal embryogenesis."Genes Cells. 6. 99-106 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chusho.H. et al: "Dwarfism and early death in mice lacking C-type natriuretic peptide."Proc Natl Acad Sri USA. 98. 4016-4021 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshimoto.R. et al: "Ca2+-Sensitization of contraction in the hi calponin-deficient smooth muscle."Jpn J Pharmacol. 84. 474-475 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi.K. et al: "Regulation of shortening velocity by calponin in intact contracting smooth muscles."Biochem Biophys Res. 279. 150-157 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukui,Y. et al: "Diversity of T cell repertoire shaped by a single peptide ligand is critically affected by its amino acid residue at a T cell receptor contact."Proc Natl Acad Sci USA. 97. 13760-13765 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato.M. et al: "bistinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-alpha/beta gene induction."Immunity. 13. 539-548 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] lse,K. et al: "Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis."Oncogene. 19. 2951-2956 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ichise.T. et al: "mGluR1 in cerebellar Purkinje cells essential for long-term depression, synapse elimination, and motor coord ination."Science. 288. 1832-1835 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murai.H. et al: "Studies of in vivo mutations in rpsL transgene in UVB-irradiated epidermis of XPA-deficient mice."Mutat Res. 450. 181-192 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shioyama.Y. et al: "Different mutation frequencies and spectra among organs by N-methyl-N-nitrosourea in rpsL (strA) transgenic mice."Jpn J Cancer Res. 91. 482-491 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] lkeda,M. et al: "PLC beta 4-independent Ca2+ rise via muscarinic receptors in the mouse suprachiasmatic nucleus."Neuroreport. 11. 907-912 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura.N. et al: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc Natl Acad Sci USA. 97. 4239-4244 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Manabe.T. et al: "Regulation of long-term potentiation by HRas through NMDA receptor phosphorylation."J Neurosci. 20. 2504-2511 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sunahara.S. et al: "The oocyte-specific methylated region of the U2afbp-rs/U2af1-rs1 gene is dispensable for its imprinted methylation."Biochem Biophys Res Commun. 268. 590-595 (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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