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Functions of signal-transducing membrane protein, gp130 in the nervous system

Research Project

Project/Area Number 11680692
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionKumamoto University (2000)
Tokyo Medical and Dental University (1999)

Principal Investigator

NAKASHIMA Kinichi  Kumamoto University Institute of Molecular Embryology and Genetics, Associate Professor, 発生医学研究センター, 助教授 (80302892)

Co-Investigator(Kenkyū-buntansha) TAGA Tetsuya  Kumamoto University Institute of Molecular Embryology and Genetics, Professor, 発生医学研究センター, 教授 (40192629)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsgp130 / neural stem cell / astrocyte / inhibition of neurogenesis / STAT / Smad / bHLH / negative HLH regulator / サイトカイン / クロストーク / p300
Research Abstract

gp130 is a signal-transducing receptor component used in common by the interleukin-6 (IL-6) family of cytokines, including IL-6, IL-11, leukemia inhibitory factor (LIF) ciliary neurotrophic factor (CNTF), oncostatin M (OSM), and cardiotrophin-1 (CT-1). When we started this project, neurotrophic role of gp130 in the nervous system had been suggested, although direct evidence indicating the importance of gp130 in the developmental and maintenance of the nervous system in vivo had not been obtained. Firstly, we have clarified in this study that gp130 supports survival of newly generated sensory and motor neurons during the late phase of development when naturally occurring cell death takes place. Secondary, We have found that LIF and bone morphogenetic protein (BMP2), which signal through distinct signaling pathways, act in synergy on cultured fetal neural progenitor cells to induce astrocytes. We have further demonstrated that respective downstream transcription factors, STAT3 and Smads, form a complex bridged by a transcriptional coactivator p300, which may explain cooperative induction of astrocytes by LIF and BMP2 from neural progenitors. Thirdly, we have shown that brief exposure to BMP2 was sufficient to change the fate of telencephalic neural progenitors in culture, from neuronal to astrocytic. BMP2 upregulated expression of negative helix-loop-helix (HLH) factors, Id1, Id3 and Hes-5, which all actually inhibited transcriptional activity of neurogenic HLH transcription factors, Mash1 and Neurogenin. Ectopic expression of either Id1 or Id3 inhibited neurogenesis from neuroepithelial cells, suggesting an important role of these negative HLH proteins in BMP2-mediated alteration of neurogenic fate of these cells.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (56 results)

All Other

All Publications (56 results)

  • [Publications] Nakashima,K., et al.: "BMP2-mediated alteration from neurogenesis to astrocytogenesis in fetal mouse brain cells"Proc.Natl.Acad.Sci.USA. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takizawa,T., et al.: "Directory linked soluble IL-6 receptor-IL-6 fusion protein induces astrocyte differentiation from neuroepithelial cells via activation of STAT3"Cytokine. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanagisawa,M., et al.: "Signaling crosstalk underlying synergistic induction of astrocyte differentiation by BMPs and IL-6 family of cytokines"FEBS Lett.. 489. 139-143 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuo,R., et al.: "A new expression cloning strategy for isolation of substrate-specific kinases by using phosphorylation site-specific antibody"J.Immunol.Methods. 247. 141-151 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanagisawa,M., et al.: "Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3"J.Neurochem.. 74. 1498-1504 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kato,H., et al.: "Identification of a Novel WD Repeat-Containing Gene Predominantly Expressed in Developing and Regenerating Neurons"J.Biochem.(Tokyo). 128. 923-932 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura,N., et al.: "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6"J.Biol.Chem.. 275. 17647-17652 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kojima,N., et al.: "Cell density-dependent regulation of hepatic development by a gp130-independent pathway"Biochem. Biophys. Res. Commun.. 277. 152-158 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ueno,M., et al.: "Genomic organization, sequence and chromosomal localization of the mouse Tbr2 gene and a comparative study with Tbr1"Gene. 254. 29-35 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamamoto,K., et al.: "Three-dimensional modeling of and ligand docking to vitamin D receptor ligand binding domain"Proc.Natl.Acad.Sci.USA. 97. 1467-1472 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamiya,A., et al.: "Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer"EMBO J.. 18. 2127-2136 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura,N., et al.: "A brain region-specific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains"J.Biochem.. 126. 180-187 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura,N., et al: "A novel mammalian T-box-containing gene, Tbr2, expressed in mouse developing brain"Brain Res.Dev.Brain Res.. 115. 183-193 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanagisawa,M., et al.: "STAT3-mediated astrocyte differentiation from mouse fetal neuroepithelial cells by mouse oncostatin M"Neurosci.Lett.. 269. 169-172 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakshima,K., et al.: "gp130-stimulating cytokines : Its signaling mechanism and roles in the nervous systems"Recent Res.Devel.Neurochem.. 2. 297-304 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakshima,K., et al.: "Astrocyte differentiation mediated by LIF in cooperation with BMP2"FEBS Lett.. 457. 43-46 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakshima,K., et al.: "Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation"J.Neurosci.. 19. 5429-5434 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakshima,K., et al.: "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300"Science. 284. 479-482 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakashima, K., Yanagisawa, M., Arakawa, H., Kimura, N., Hisatsune, T., Kawabata, M., Miyazono, K., and Taga, T.: "Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300."Science. 284. 479-482 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakashima, K., Wiese, S., Yanagisawa, M., Arakawa, H., Kimura, N., Hisatsune, T., Yoshida, K., Kishimoto, T., Sendtner, M., and Taga, T.: "Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation."J Neurosci. 19. 5429-5434 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakashima, K., Yanagisawa, M., Arakawa, H., and Taga, T.: "Astrocyte differentiation mediated by LIF in cooperation with BMP2."FEBS Lett. 457. 43-46 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakashima, K., and Taga, T.: "gp130-stimulating cytokines : Its signaling mechanism and roles in the nervous systems."Recent Res Devel Neurochem. 2. 297-304 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanagisawa, M., Nakashima, K., and Taga, T.: "STAT3-mediated astrocyte differentiation from mouse fetal neuroepithelial cells by mouse oncostatin M."Neurosci Lett. 269. 169-172 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura, N., Nakashima, K., Ueno, M., Kiyama, H., and Taga, T.: "A novel mammalian T-box-containing gene, Tbr2, expressed in mouse developing brain."Brain Res Dev Brain Res. 115. 183-193 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura, N., Ueno, M., Nakashima, K., and Taga, T.: "A brain regionspecific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains."J Biochem. 126. 180-187 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kamiya, A., Kinoshita, T., Ito, Y., Matsui, T., Morikawa, T., Senba, E., Nakashima, K., Taga, T., Yoshida, K., Kishimoto, T., and Miyajima, A.: "Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer."EMBOJ. 18. 2127-2136 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamamoto, K., Masuno, H., Choi, M., Nakashima, K., Taga, T., Ooizumi, H., Umesono, K., Sicinska, W., VanHooke, J., DeLuca, H.F., and Yamada, S.: "Three-dimensional modeling of and ligand docking to vitamin D receptor ligand binding domain."Proc Natl Acad Sci USA. 97. 1467-1472 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanagisawa, M., Nakashima, K., Arakawa, H., Ikenaka, K., Yoshida, K., Kishimoto, T., Hisatsune, T., and Taga, T.: "Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3."J Neurochem. 74. 1498-1504 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chijiwa, T., Deshimaru, M., Nobuhisa, I., Nakai, M., Ogawa, T., Oda, N., Nakashima, K., Fukumaki, Y., Shimohigashi, Y., Hattori, S., and Ohno, M.: "Regional evolution of venom-gland phospholipase A2 isoenzymes of Trimeresurus flavoviridis snakes in the southwestern islands of Japan."Biochem J. 347. 491-499 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kato, H., Chen, S., Kiyama, H., Ikeda, K., Kimura, N., Nakashima, K., and Taga, T.: "Identification of a Novel WD Repeat-Containing Gene Predominantly Expressed in Developing and Regenerating Neurons."J Biochem. 128. 923-932 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura, N., Matsuo, R., Shibuya, H., Nakashima, K., and Taga, T.: "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6."J Biol Chem. 275. 17647-17652 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kojima, N., Kinoshita, T., Kamiya, A., Nakamura, K., Nakashima, K., Taga, T., and Miyajima, A.: "Cell density-dependent regulation of hepatic development by a gp130-independent pathway."Biochem Biophys Res Commun. 277. 152-158 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ueno, M., Kimura, N., Nakashima, K., Saito-Ohara, F., Inazawa, J., and Taga, T.: "Genomic organization, sequence and chromosomal localization of the mouse Tbr2 gene and a comparative study with Tbr1."Gene. 254. 29-35 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuo, R., Ochiai, W., Nakashima, K., and Taga, T.: "A new expression cloning strategy for isolation of substrate-specific kinases by using phosphorylation site-specific antibody."J Immunol Methods. 247. 141-151 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yanagisawa, M., Nakashima, K., Takizawa, T., Ochiai, W., Arakawa, H., and Taga, T.: "Signaling crosstalk underlying synergistic induction of astrocyte differentiation by BMPs and IL-6 family of cytokines."FEBS Lett. 489. 139-143 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takizawa, T., Yanagisawa, M., Ochiai, W., Yasukawa, K., Ishiguro, T., Nakashima, K., and Taga, T.: "Directly linked soluble IL-6 receptor-IL-6 fusion protein induces astrocyte differentiation from neuroepithelial cells via activation of STAT3."Cytokine. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakashima, K., Takizawa, T., Ochiai, W., Yanagisawa, M., Hisatsune, T., Nakafuku, M., Miyazomo, K., Kishimoto, T., Kageyama, R., and Taga, T.: "BMP2-mediated alteration from neurogenesis to astrocytogenesis in fetal mouse brain cells."Proc Natl Acad Sci USA. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakashima,K.,Takizawa,T.,(中略7) Taga,T.: "BMP2-mediated alteration from neurogenesis to astrocytogenesis in fetal mouse brain cells"Proc.Natl.Acad.Sci.USA. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Takizawa,T.,(中略4) Nakashima,K.,Taga,T.: "Directory linked soluble IL-6 receptor-IL-6 fusion protein induces astrocyte differentiation from neuroepithelial cells via activation of STAT3"Cytokine. (In press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yanagisawa,M.,Nakashima,K.,(中略3) Taga,T.: "Signaling crosstalk underlying synergistic induction of astrocyte differentiation by BMPs and IL-6 family of cytokines"FEBS Lett.. 489. 139-143 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuo,R.,Ochiai,W.,Nakashima,K.,Taga,T.: "A new expression cloning strategy for isolation of substrate-specific kinases by using phosphorylation site-specific antibody"J.Immunol.Methods. 247. 141-151 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yanagisawa,M.,Nakashima,K.,(中略5) Taga,T.: "Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer,gp130, and a transcription factor, STAT3"J.Neurochem.. 74. 1498-1504 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kato,H.,(中略4) Nakashima,K.,Taga,T.: "Identification of a Novel WD Repeat-Containing Gene Predominantly Expressed in Developing and Regenerating Neurons"J.Biochem.(Tokyo). 128. 923-932 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kimura,N.,(中略2) Nakashima,K.,Taga,T.: "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6"J.Biol.Chem.. 275. 17647-17652 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kojima,N.(中略3) Nakashima,K.,Taga,T.,Miyajima,A.: "Cell density-dependent regulation of hepatic development by a gp130-independent pathway"Biochem.Biophys.Res.Commun.. 277. 152-158 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueno,M.,Kimura,N.,Nakashima,K.,(中略2) Taga,T.: "Genomic organization, sequence and chromosomal localization of the mouse Tbr2 gene and a comparative study with Tbr1"Gene. 254. 29-35 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamoto,K.,(中略2) Nakashima,K.,Taga,T.(後略6): "Three-dimensional modeling of and ligand docking to vitamin D receptor ligand binding domain"Proc.Natl.Acad.Sci.USA. 97. 1467-1472 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakashima K, (中略6) Taga T: "Synergistic signaling in fetal brain by STST3-Smad1 complex bridged by p300"Science. 284. 479-482 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakashima K, (中略8) Taga T: "Developmental requirement of gp130 signaling in neuronal survival and astrocyte differentiation"J. Neurosci.. 19. 5429-5434 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakashima K, (中略2) Taga T: "Astrocyte differentiation mediated by LIF in cooperation with BMP2"FEBS Lett.. 457. 43-46 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakashima K, Taga T: "gp130-stimulating cytokines: Its signaling mechanism and roles in the nervous systems"Recent Res. Devel. Neurochem.. 2. 297-304 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yanagisawa M, Nakashima K, Taga T: "STAT3-mediated astrocyte differentiation from mouse fetal neuroepithelial cells by mouse oncostatin M"Neurosci. Lett.. 269. 169-172 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kimura N, Nakashima K, (中略2) Taga T: "A novel mammaliam T-box-containing gene, Tbr2, expressed in mouse developing brain"Dev. Brain Res.. 115. 183-193 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kimura N, Ueno M, Nakashima K, Taga T: "A brain-region specific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains"J. Biochem.. 126. 180-187 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kamiya A, (中略5) Nakashima K, Taga T, (後略3): "Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer"EMBO J.. 18. 2127-2136 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yanagisawa M, Nakashima K, (中略5) Taga T: "Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription facter, STAT3"J. Neurochem.. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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