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2005 Fiscal Year Final Research Report Summary

Regulatory Mechanisms of the Activity of Pax6 that Controls Cell Differentiation

Research Project

Project/Area Number 16370093
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionKyoto University (2005)
Biomolecular Engineering Research Institute (BERI) (2004)

Principal Investigator

OKAZAKI Kenji  Kyoto University, Graduate School of Science, Research Scientist, 大学院・理学研究科, 研究員(科学研究) (50211115)

Co-Investigator(Kenkyū-buntansha) AOTA Shinichi  Osaka University, Graduate School of Frontier Biosciences, Research Scholar, 生命機能研究科, 特任研究員 (50192456)
Project Period (FY) 2004 – 2005
KeywordsCell differentiation / Pax6 / Regulation of activity / Paired-domain / LE9 / Phosphorylation of transcription factors
Research Abstract

By using LE9 enhancer element, a target DNA fragment directly bound by Pax6 protein, that is present in the head surface ectoderm-specific enhancer region of the pax6 gene and is responsive to the autoreguration of the pax6 gene expression, we studied regulatory mechanisms of Pax6 protein through its phosphorylation. Our result showed that the activity of Pax6 toward LE9 is highly elevated by ERK_<1/2> or p38MAPK. We identified four phosphorylation sites in the carboxy terminal domain, among which the three sites were able to be directly phosphorylated by p38MAPK in vitro. Furthermore, a Ser-to-Ala mutation of one of these residue resulted in a suppression of the transcriptional response to the activation of the kinase pathways. Because the phosphorylation of Pax6 had little influence to the stability of Pax6 protein, the phosphorylated sites seems to operate by interacting with other factors to contribute to the transcriptional activation of LE9. Analyses of the phosphorylation pattern of in vivo Pax6 became possible by preparation of monoclonal antibodies specific for an amino acid sequence containing the phosphorylated residue. Whereas a growth signal-induced increase of the phosphorylation of nuclear Pax6 supported the significance of ERK pathway, its sustained phosphorylation suggested an involvement of another kinase. Above results demonstrated that the function of Pax6 is regulated by the phosphorylation of its C-terminal domain and that this control is dependent on the MAP kinase pathways. It Will be an important issue to clarify the mechanisms for phosphorylation signaling in the differentiation process of eyes, in which LE9 enhancer is considered to really function.

  • Research Products

    (8 results)

All 2005 2004

All Journal Article (6 results) Book (2 results)

  • [Journal Article] Crystallization and preliminary X-ray analysis of the Pax6 paired domain bound to the Pax6 gene enhancer2005

    • Author(s)
      Ito, M., et al.
    • Journal Title

      Acta Crystallographica F61

      Pages: 1009-1012

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Smad7 induces the G0/G1 cell cycle arrest in mesenchymal cells by inhibiting the expression of G1 cyclins2005

    • Author(s)
      Kitamura, K., et al.
    • Journal Title

      Development Growth & Differentiation 47

      Pages: 537-552

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Crystallization and preliminary X-ray analysis of the Pax6 paired domain bound to the Pax6 gene enhancer2005

    • Author(s)
      Ito, M., et al.
    • Journal Title

      Acta Crystallographica F16

      Pages: 1009-1012

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Smad7 induces the G0/G1 cell cycle arrest in mesenchymal cells by inhibiting the expression of G1 cyclins2005

    • Author(s)
      Kitamura K., Aota, S., Sakamoto, R., Emori, T., Okazaki, K.
    • Journal Title

      Development Growth & Differentiation 47

      Pages: 537-552

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] BMP signaling through ACVRI is required for left-right patterning in the early mouse embryo2004

    • Author(s)
      Kishigami, S., et al.
    • Journal Title

      Developmental Biology 276

      Pages: 185-193

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Craniofacial defects in mice lacking BMP type I receptor Alk2 in neural crest cells2004

    • Author(s)
      Dudas, M., et al.
    • Journal Title

      Mechanisms of Development 121

      Pages: 173-182

    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 生命の謎を解く(関口睦夫 編)2004

    • Author(s)
      岡崎賢二 他
    • Total Pages
      177
    • Publisher
      共立出版
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Solving the Mysteries of Life(ISBN4-320-05614-0, ed.Sekiguchi, M.)2004

    • Author(s)
      Okazaki, K., et al.
    • Publisher
      Kyoritsu Publishing Co.Tokyo
    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2007-12-13  

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