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Clarification of the function and regulation of the rheostat molecule NLK, which fine-tunes the activity strength of signal transduction.

Research Project

Project/Area Number 22689008
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionKyushu University

Principal Investigator

ISHITANI Tohru  九州大学, 生体防御医学研究所, 准教授 (40448428)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2011: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2010: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywordsリン酸化 / 器官形成 / がん / イメージング / NLK / Wntシグナル / Notchシグナル / シグナルレオスタット / Nemo-like kinase / ホモダイマー形成 / Lef1
Research Abstract

NLK is an evolutionarily conserved protein kinase, which fine-tunes the activity strength of various signal transduction systems. In this study, we discovered that NLK strengthen Wnt signaling activity by phosphorylating a transcription factor Lef1 in neural progenitor cells and this regulation contributes to the size expansion of vertebrate brain tissues. We also found that NLK autoactivates via its autophosphorylation and that DP1 protein inhibits NLK activity. Thus, we revealed new functions and regulations of NLK.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (51 results)

All 2013 2012 2011 2010 Other

All Journal Article (8 results) (of which Peer Reviewed: 5 results) Presentation (34 results) (of which Invited: 1 results) Book (5 results) Remarks (4 results)

  • [Journal Article] NLK positively regulates Wnt/β-catenin signaling by phosphorylating LEF1 in neural progenitor cells2012

    • Author(s)
      Ota, S., Ishitani, S., Shimizu, N., Matsumoto, K., Itoh, M., and Ishitani. T
    • Journal Title

      EMBO J

      Volume: 31 Issue: 8 Pages: 1904-1915

    • DOI

      10.1038/emboj.2012.46

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Context-dependent dual and opposite roles of nemo-like kinase in the Wnt/β-catenin signaling2012

    • Author(s)
      Ishitani T
    • Journal Title

      Cell Cycle

      Volume: 11 Issue: 9 Pages: 1743-1745

    • DOI

      10.4161/cc.20183

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Journal Article] Visualization and exploration of Tcf/Lef function using a highly responsive Wnt/β-catenin signaling-reporter transgenic zebrafish2012

    • Author(s)
      Shimizu N, Kawakami K, *Ishitani T
    • Journal Title

      Developmental Biology

      Volume: 370. Issue: 1 Pages: 71-85

    • DOI

      10.1016/j.cellsig.2012.09.017

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dual functions of DP1 promote and stabilize biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning.2012

    • Author(s)
      Kim WT, Kim H, Katanaev VL, Joon Lee S, Ishitani T, Cha B, Han JK, *Jho EH.
    • Journal Title

      EMBO Journal

      Volume: 31. Issue: 7 Pages: 3384-3397

    • DOI

      10.1038/emboj.2012.18

    • Related Report
      2012 Final Research Report
  • [Journal Article] Dual functions of DP1 promote biphasic Wnt-on and Wnt-off states during anteroposterior neural patterning.2012

    • Author(s)
      Kim WT, Kim H, Katanaev VL, Joon Lee S, Ishitani T, Cha B, Han JK, Jho EH.
    • Journal Title

      EMBO Journal

      Volume: 31 Issue: 16 Pages: 3384-3397

    • DOI

      10.1038/emboj.2012.181

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visualization and exploration of Tcf/Lef function using a highly responsive Wnt/β-catenin signaling-reporter transgenic zebrafish.2012

    • Author(s)
      Shimizu N, Kawakami K, Ishitani T.
    • Journal Title

      Developmental Biology

      Volume: 370 Issue: 1 Pages: 71-85

    • DOI

      10.1016/j.ydbio.2012.07.016

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homo-dimerization of Nemo-like kinase is essential for activation and nuclear localization2011

    • Author(s)
      Ishitani S, Inaba K, Matsumoto K, *Ishitani T.
    • Journal Title

      Molecular Biology of the Cel

      Volume: 22 Pages: 266-277

    • NAID

      120004979399

    • Related Report
      2012 Final Research Report
  • [Journal Article] Homo-dimerization of Nemo-like kinase is essential for activation and nuclear localization2011

    • Author(s)
      Ishitani S, Inaba K, Matsumoto K, Ishitani T.
    • Journal Title

      Molecular Biology of the Cell

      Volume: 22 Pages: 266-277

    • NAID

      120004979399

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Roles of two Ser/The kinases, NLK and Hipk2, in the regulation of Wnt/β-catenin signaling2013

    • Author(s)
      Tohru Ishitani
    • Organizer
      1st International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
    • Place of Presentation
      The Auditorium The Institute of Medical Science, The University of Tokyo
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Nemo-like kinase Blocks Hedgehog signaling by phosphorylating Gli1 transcription factor.2012

    • Author(s)
      石谷 太, 清水 誠之, 石谷 閑
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2012-12-16
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] Exploration of Tcf/Lef function using a highly responsive Wnt/β-catenin signaling-reporter transgenic zebrafish2012

    • Author(s)
      Nobuyuki Shimizu, Koichi Kawakami, Tohru Ishitani
    • Organizer
      第18回小型魚類研究会
    • Place of Presentation
      京都大学
    • Year and Date
      2012-09-22
    • Related Report
      2012 Final Research Report
  • [Presentation] NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells2012

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, To hru Ishitani
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2012-09-19
    • Related Report
      2012 Final Research Report
  • [Presentation] A dual and opposite role of NLK-mediated Lef1 phosphorylation on the Wnt/beta-catenin signaling2012

    • Author(s)
      Tohru Ishitani, Shizuka Ishitani
    • Organizer
      第45回日本発生生物学会・第64回日本細胞生物学会合同年会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2012-05-31
    • Related Report
      2012 Final Research Report
  • [Presentation] NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells.2012

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] A dual and opposite role of NLK-mediated Lef1 phosphorylation on the Wnt/β-catenin signaling2012

    • Author(s)
      Tohru Ishitani, Shizuka Ishitani
    • Organizer
      第45回日本発生生物学会・第64回日本細胞生物学会 合同年会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] Nemo-like kinase regulates its own activity by sequential autophosphorylation2012

    • Author(s)
      Shizuka Ishitani, Tohru Ishitani
    • Organizer
      第45回日本発生生物学会・第64回日本細胞生物学会 合同年会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] NLK positively regulates Wnt⁄β-catenin signalling by phosphorylating LEF1 in neural progenitor cells.2012

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani
    • Organizer
      the 10th International Conference on Zebrafish Development and Genetics
    • Place of Presentation
      Madison, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Live imaging of Tcf/Lef activity in developing, growing, and regenerating tissues of the highly responsive Wnt/β-catenin signaling reporter-transgenic zebrafish2012

    • Author(s)
      Nobuyuki Shimizu and Tohru Ishitani
    • Organizer
      the 10th International Conference on Zebrafish Development and Genetics
    • Place of Presentation
      Madison, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells.2012

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani
    • Organizer
      EMBO conference 30 years of Wnt signaling
    • Place of Presentation
      Egmond Aan Zee, Netherlands
    • Related Report
      2012 Annual Research Report
  • [Presentation] Exploration of Tcf/Lef function using a highly responsive Wnt/β-catenin signaling-reporter transgenic zebrafish2012

    • Author(s)
      Nobuyuki Shimizu, Koichi Kawakami, and Tohru Ishitani
    • Organizer
      第18回小型魚類研究会
    • Place of Presentation
      京都大学芝蘭会館
    • Related Report
      2012 Annual Research Report
  • [Presentation] Lef1 phosphorylation by NLK is essential for the Lef1-mediated Wnt/β-catenin signaling in neural progenitor cells2011

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-12-16
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] Analysis of the molecular mechanisms that regulate the activity of Nemo-like kinase2011

    • Author(s)
      Shizuka Ishitani, Tohru Ishitani
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2011-12-15
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] Analysis of the spatiotemporal dynamics and its regulatory mechanisms of Wnt/β-catenin and Hedgehog signaling pathways using the transgenic zebrafish lines carrying the signaling reporters.2011

    • Author(s)
      Nobuyuki Shimizu, Tohru Ishitani
    • Organizer
      第17回小型魚類研究会
    • Place of Presentation
      東レ総合研修センター
    • Year and Date
      2011-09-08
    • Related Report
      2012 Final Research Report
  • [Presentation] Analysis of the spatiotemporal dynamics and its regulatory mechanisms of Wnt/β-catenin and Hedgehog signaling pathways using the transgenic zebrafish lines carrying the signaling reporters2011

    • Author(s)
      Nobuyuki Shimizu, Tohru Ishitani
    • Organizer
      第17回小型魚類研究会
    • Place of Presentation
      三島市東レ研修センター
    • Year and Date
      2011-09-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] Homo-dimerization of Nemo-like kinase is essential for activation and nuclear localization.2011

    • Author(s)
      Shizuka Ishitani, Kenji Inaba, Kunihiro Matsumoto, Tohru Ishitani
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      北海道大学
    • Year and Date
      2011-06-28
    • Related Report
      2012 Final Research Report
  • [Presentation] Homo-dimerization of Nemo-like kinase is essential for activation and nuclear localization2011

    • Author(s)
      Shizuka Ishitani, Kenji Inaba, Kunihiro Matsumoto, Tohru Ishitani
    • Organizer
      第63回日本細胞生物学会大会
    • Place of Presentation
      北海道大学
    • Year and Date
      2011-06-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Lef1 phosphorylation by NLK is essential for the Lef1-mediated Wnt/β-catenin signaling in neural progenitor cells2011

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani
    • Organizer
      沖縄コンベンションセンター, 第44回日本発生生物学会
    • Year and Date
      2011-05-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Lef1 phosphorylation by NLK is essential for the Lef1-mediated Wnt/β-catenin signaling in neural progenitor cells2011

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani
    • Organizer
      第44回日本発生生物学会
    • Place of Presentation
      沖縄コンベンションセンター
    • Year and Date
      2011-05-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] Lef1 phosphorylation by NLK is essential for the Lef1-mediated Wnt/β-catenin signaling in Neural progenitor cells2011

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, To hru Ishitani
    • Organizer
      4th Strategic Conference of Zebrafish Investigators
    • Place of Presentation
      Asilomar Conference Center, USA
    • Year and Date
      2011-01-31
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] NLKによるLef1のリン酸化は神経前駆細胞におけるWnt/β-cateninシグナルの伝達に必須である2010

    • Author(s)
      太田聡、石谷閑、清水誠之、松本邦弘、伊藤素行、石谷太
    • Organizer
      BMB2010
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] ゼブラフィッシュ生個体におけるWnt シグナルの活動の時空間的動態の可視化2010

    • Author(s)
      清水 誠之、太田 聡、石谷 太
    • Organizer
      BMB2010
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-12-07
    • Related Report
      2012 Final Research Report
  • [Presentation] NLKによるLef1のリン酸化は、神経前駆細胞におけるWnt/β-cateninシグナルの伝達に必須である2010

    • Author(s)
      太田 聡、石谷 閑、清水 誠之、松本邦弘、伊藤素行、石谷 太
    • Organizer
      BMB2010
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-12-07
    • Related Report
      2012 Final Research Report
  • [Presentation] ゼブラフィッシュ生個体におけるWntシグナルの活動の時空間的動態の可視化2010

    • Author(s)
      清水誠之、太田聡、五谷太
    • Organizer
      BMB2010
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] 神経細胞におけるWnt-β カテニン経路の活性化には、NLK による転写因子Lef1 のリン酸化が必須である2010

    • Author(s)
      太田 聡、石谷 閑、清水 誠之、松本邦弘、伊藤素行、石谷 太
    • Organizer
      第16回小型魚類研究会
    • Place of Presentation
      埼玉
    • Year and Date
      2010-09-18
    • Related Report
      2012 Final Research Report
  • [Presentation] ゼブラフィッシュにおけるWnt シグナルの活動の時空間的動態の可視化2010

    • Author(s)
      清水 誠之、太田 聡、石谷 太
    • Organizer
      第16回小型魚類研究会
    • Place of Presentation
      埼玉
    • Year and Date
      2010-09-18
    • Related Report
      2012 Final Research Report
  • [Presentation] Nemo-like kinase promotes neurogenesis by interfering with formation of Notch Vanscnption complex.2010

    • Author(s)
      Tohru Ishitani, Tomoko Hirao, Maho Suzuki, Miho Isoda, Shizuka Ishitani, Motoo Kitagawa, Kunihiro Matsumoto, Motoyuki Itoh
    • Organizer
      Neuro-2010
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nemo-like kinase promotes neurogenesis by interfering with formation of Notch transcription complex.2010

    • Author(s)
      Tohru Ishitani, Tomoko Hirao, Maho Suzuki, Miho Isoda, Shizuka Ishitani, Motoo Kitagawa, Kunihiro Matsumoto, & Motoyuki Itoh
    • Organizer
      第43回日本発生生物学会大会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2010-06-22
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] Nemo-like kinase positively regulates Wnt signaling via phosphorylating Lef1 in developing midbrain tectum2010

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani
    • Organizer
      第43回日本発生生物学会大会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2010-06-20
    • Related Report
      2012 Final Research Report
  • [Presentation] Nemo-like kinase positively regulates Wnt signaling via phosphorylating Lefl in developing midbrain tectum.2010

    • Author(s)
      Satoshi Ota, Shizuka Ishitani, Nobuyuki Shimizu, Kunihiro Matsumoto, Motoyuki Itoh, Tohru Ishitani
    • Organizer
      第43回日本発生生物学会大会
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2010-06-20
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nemo-like kinase promotes neurogenesis by interfering with formation of Notch transcription complex2010

    • Author(s)
      Tohru Ishitani, Tomoko Hirao, Maho Suzuki, Miho Isoda, Shizuka Ishitani, Motoo Kitagawa, Kunihiro Matsumoto, & Motoyuki Itoh
    • Organizer
      9th International Zebrafish Development and Genetics Conference
    • Place of Presentation
      Wisconsin, USA
    • Year and Date
      2010-06-17
    • Related Report
      2012 Final Research Report
  • [Presentation] Nemo-like kinase promotes neurogenesis by interfering with formation of Notch transcription complex.2010

    • Author(s)
      Tohru Ishitani, Tomoko Hirao, Maho Suzuki, Miho Isoda, Shizuka Ishitani Motoo Kitagawa, Kunihiro Matsumoto, Motoyuki Itoh
    • Organizer
      9th International Zebrafish Development and Genetics Conference
    • Place of Presentation
      Wisconsin, USA
    • Year and Date
      2010-06-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Nemo-like kinaseはNotch転写複合体の形成を阻害することによりNotchシグナルを抑制する2010

    • Author(s)
      石谷 太、石谷 閑、 平尾 智子、鈴木 真帆、磯田 美帆、北川 元生、松本 邦弘、伊藤 素行
    • Organizer
      第62回日本細胞生物学会年会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-05-19
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Book] 神経組織構築を担うタンパク質リン酸化酵素NLKの機能と制御ブレインサイエンス・レビュ2012

    • Author(s)
      石谷太
    • Related Report
      2012 Final Research Report
  • [Book] 実験医学 Nemo-like kinaseはNotch転写複合体の形成を阻害し、神経細胞形成を促進する2010

    • Author(s)
      石谷太,松本邦弘, 伊藤素行
    • Related Report
      2012 Final Research Report
  • [Book] 医学のあゆみ 転写因子TCF/LEFの修飾によるWntシグナル制御2010

    • Author(s)
      石谷太,石谷閑.
    • Related Report
      2012 Final Research Report
  • [Book] 実験医学カレントトピックス「Nemo-like kinaseはNotch転写複合体の形成を阻害し神経細胞形成を促進する」2010

    • Author(s)
      石谷太, 松本邦弘, 伊藤素行
    • Total Pages
      4
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Book] 医学のあゆみ「転写因子TCF/LEFの修飾によるWntシグナル制御」2010

    • Author(s)
      五谷太, 石谷閑
    • Total Pages
      8
    • Publisher
      医歯薬出版
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.bioreg.kyushu-u.ac.jp/labo/crs/top.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 石谷研究室プログレス

    • URL

      http://www.bioreg.kyushu-u.ac.jp/labo/crs/sub11.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.bioreg.kyushu-u.ac.jp/labo/crs/sub11.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.bioreg.kyushu-u.ac.jp/labo/crs/sub11.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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