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Relationship between islet b-cell failure and phosphorylation of b-cell specific transcription factor MafA

Research Project

Project/Area Number 25461353
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionYokohama City University

Principal Investigator

Kataoka Kohsuke  横浜市立大学, 生命医科学研究科, 准教授 (20262074)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords糖尿病 / 細胞内シグナル伝達 / 遺伝子発現制御 / 膵β細胞機能不全 / リン酸化 / 転写制御因子 / シグナル伝達 / 遺伝子発現
Outline of Final Research Achievements

During progression of type-2 diabetes, pancreatic islet b-cells gradually lose their ability to produce and secrete Insulin in response to high blood glucose. To clarify molecular mechanism of the b-cell failure, I analyzed function and activity of b-cell specific transcription factor MafA in b-cells during diabetes progression.
I found that multiple phosphorylation events on MafA regulates its interaction with Beta2, another important transcriptional regulator of b-cell function. I also found that multiple protein kinases phosphorylate MafA redundantly. In b-cells of type-2 diabetes model mice db/db, intracellular distribution and/or abundance of these kinases change during progression of diabetes. Elucidating the mechanism of regulation of these kinases in b-cells may lead to understanding of b-cell failure and contribute to prevention and treatment of diabetes .

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (6 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Phosphorylation of MafA enhances interaction with Beta2/NeuroD1.2016

    • Author(s)
      Han, S.-i, Y. Tsunekage, K. Kataoka
    • Journal Title

      Acta Diabetologica

      Volume: - Issue: 4 Pages: 651-660

    • DOI

      10.1007/s00592-016-0853-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Transcription Factor MafB coordinates epidermal keratinocyte differentiation.2016

    • Author(s)
      M. Miyai, M. Hamada, T. Moriguchi, J. Hiruma, A. Kamitani-Kawamoto, H Watanabe, M. Hara-Chikuma, K. Takahashi, S. Takahashi, K Kataoka
    • Journal Title

      Journal of Investigative Dermatology

      Volume: -

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP12015

    • Author(s)
      SI. Han, Y. Tsunekage and K. Kataoka
    • Journal Title

      Molecular and Cellular Endocrinology

      Volume: 409 Pages: 113-120

    • DOI

      10.1016/j.mce.2015.04.018

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis2014

    • Author(s)
      N. suda, T. Itoh, R. Nakato et. al.
    • Journal Title

      Development

      Volume: 141 Issue: 14 Pages: 2885-2894

    • DOI

      10.1242/dev.099150

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵島β細胞特異的転写因子MafAの多重リン酸化による細胞増殖制御機構2015

    • Author(s)
      金井賢一、片岡浩介
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Gata3はSP1との相互作用を介してMafB及びGcm2と協調的に副甲状腺ホルモン遺伝子の発現を活性化する2015

    • Author(s)
      韓松伊、常陰幸乃、片岡浩介
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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