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Identification and characterization of novel kinase, AKB14-3-3-1, which is a possible target of sleeping sickness.

Research Project

Project/Area Number 23590500
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Parasitology (including Sanitary zoology)
Research InstitutionKurume University

Principal Investigator

INOUE Masahiro  久留米大学, 医学部, 教授 (00232562)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsTb14-3-3 / 蛋白リン酸化酵素 / 細胞分裂 / 細胞骨格 / リン酸化モチーフ / kinase substrate Ab / cytokinesis / inhibitor / complex / AKB14-3-3-1 / Trypanosoma brucei / 14-3-3 / kinase / cell division / 2014/3/3 / cell divison
Research Abstract

Proteomics approach of searching Tb14-3-3 binding proteins identified a novel associated kinase of Tb14-3-3 (AKB1). Tb14-3-3 directly and specifically binds to AKB1 utilizing an amphipathic groove structure of Tb14-3-3. Critical amino acid motif forAKB1 substrate recognition was identified and in vivo AKB1 kinase activity was successfully monitored with phosphorylated substrate-specific antibody. Majority of AKB1 is associated with cytoskeleton and most of AKB1 substrates are also identified in the detergent-insoluble fraction of cell lysate. AKB1 knockdown or overexpression of wild type AKB1 but not kinase-dead AKB1, deregulated cytokinesis and cell division, suggesting that kinase activity of AKB1 is crucial for growth. The results from this study suggest that AKB1 associated with Tb14-3-3 modulates cytokinesis and cell cycle progression in Trypanosoma brucei by phosphorylating cytoskeleton-associated proteins.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (15 results)

All 2014 2013 2012 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (13 results)

  • [Journal Article] Trypanosoma brucei 14-3-3I and II proteins predominantly form a heterodimer structure that acts as a potent cell cycle regulator in vivo.2013

    • Author(s)
      Inoue M
    • Journal Title

      J. Biochem.

      Volume: 153(5) Issue: 5 Pages: 431-439

    • DOI

      10.1093/jb/mvt016

    • NAID

      40019646817

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible role of inter-domain salt bridges in oligopeptidase B from Trypanosoma brucei: critical role of Glu172 of non-catalytic β-propeller domain in catalytic activity and Glu490 of catalytic domain in stability of OPB.2013

    • Author(s)
      Fukumoto J, Ismail NI, Kubo M, Kinoshita K, Inoue M, Yuasa K, Nishimoto M, Matsuki H, Tsuji A.
    • Journal Title

      J. Biochem.

      Volume: 154 Issue: 5 Pages: 465-473

    • DOI

      10.1093/jb/mvt077

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 消化管寄生線虫の急性感染と慢性感染の混合感染による相互作用2014

    • Author(s)
      石渡賢治
    • Organizer
      第83回日本寄生虫学会大会
    • Place of Presentation
      松山市
    • Year and Date
      2014-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] AKB1(associated kinase of Tb14-3-3-1)のin vitro酵素活性2014

    • Author(s)
      井上雅広、安田幸一、上村春樹
    • Organizer
      第83回日本寄生虫学会大会
    • Place of Presentation
      愛媛大学城北キャンパス(愛媛県松山市)
    • Year and Date
      2014-03-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Antigen-presenting cell responses of mesenteric lymph nodes in mice infected with a gastrointestinal nematode, Nippostrongylus brasiliensis2014

    • Author(s)
      Ishiwata-K
    • Organizer
      13th International Symposium on Dendritic Cells
    • Place of Presentation
      Loire Valley, France
    • Related Report
      2013 Final Research Report
  • [Presentation] AKB1(associated kinase of Tb14-3-3-1) のin vitro 酵素活性2014

    • Author(s)
      井上雅広、安田幸一、上村春樹
    • Organizer
      第83回日本寄生虫学会大会
    • Place of Presentation
      愛媛大学 城北キャンパス(愛媛県松山市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Antigen-presenting cell responses in mesenteric lymph nodes of mice infected with gastrointestinal nematodes2013

    • Author(s)
      Ishiwata-K
    • Organizer
      日本免疫学会総会・学術集会
    • Place of Presentation
      千葉市
    • Year and Date
      2013-12-13
    • Related Report
      2013 Final Research Report
  • [Presentation] 14-3-3タンパク質によるDAPK2活性制御機構の解析2013

    • Author(s)
      太田玲奈、松田真弥、井上雅広、辻明彦、湯浅恵造
    • Organizer
      第54回日本生化学会中国・四国支部例会
    • Place of Presentation
      徳島大学大塚講堂(徳島市)
    • Year and Date
      2013-06-01
    • Related Report
      2013 Final Research Report
  • [Presentation] Tb14-3-3によるAKB14-3-3-1の蛋白リン酸化制御2013

    • Author(s)
      井上雅広
    • Organizer
      第82回日本寄生虫学会大会
    • Place of Presentation
      東京医科歯科大学湯島キャンパス(東京都)
    • Year and Date
      2013-03-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 14-3-3タンパク質によるDAPK2活性制御機構の解析2013

    • Author(s)
      太田玲奈
    • Organizer
      第54回(平成25年度)日本生化学会中国・四国支部例会
    • Place of Presentation
      徳島大学 大塚講堂(徳島市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Tb14-3-3によるAKB14-3-3-1の蛋白リン酸化制御2013

    • Author(s)
      井上雅広
    • Organizer
      第82回日本寄生虫学会大会
    • Place of Presentation
      東京医科歯科大学 湯島キャンパス(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] Associated kinase of Trypansoma brucei 14-3-3(AKB1)の分子生物学2012

    • Author(s)
      井上雅広
    • Organizer
      第72回日本寄生虫学会大会東日本支部会・第10回分子寄生虫マラリアフォーラム合同大会
    • Place of Presentation
      群馬大学医学部刀城会館(前橋市)
    • Year and Date
      2012-10-13
    • Related Report
      2013 Final Research Report
  • [Presentation] AKB14-3-3 (Associated kinase of Trypansoma brucei 14-3-3)2012

    • Author(s)
      井上雅広
    • Organizer
      第81回日本寄生虫学会大会
    • Place of Presentation
      兵庫医科大学西宮キャンパス(西宮市)
    • Year and Date
      2012-03-24
    • Related Report
      2013 Final Research Report
  • [Presentation] Associated kinase of Trypanosoma brucei 14-3-3-1(AKB1)の分子生物学2012

    • Author(s)
      井上雅広
    • Organizer
      第10回分子寄生虫マラリアフォーラム合同大会
    • Place of Presentation
      群馬大学医学部 刀城会館(前橋市)
    • Related Report
      2012 Research-status Report
  • [Presentation] AKB14-3-3 (Associated kinase of Trypanosoma brucei 14-3-3)

    • Author(s)
      井上雅広
    • Organizer
      第81回日本寄生虫学会大会
    • Place of Presentation
      兵庫医科大学
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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