• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Investigation of the medical/biological roles of the parafibromin functions regulated by SHP2 oncoprotein

Research Project

Project/Area Number 15K18399
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionThe University of Tokyo

Principal Investigator

TAKAHASHI Atsushi  東京大学, 大学院医学系研究科(医学部), 助教 (00624496)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsParafibromin / チロシン脱リン酸化酵素SHP2 / Wntシグナル伝達経路 / YAP / 選択的スプライシング / SHP2 / PTK6 / YAP/TAZ
Outline of Final Research Achievements

(1) It was suggested that deregulated tyrosine-dephosphorylation of Parafibromin caused lethal defects in embryogenesis of mice. We reported that tyrosine-dephosphorylated form of Parafibromin acts as a coactivator of the Wnt/Hedgehog/Notch signaling pathways, which play crucial roles in morphogenesis.
(2) Loss of function of the leucine-zipper motif lost the SHP2-binding ability of the YAP isoform that possesses the exon 6-encoded γ-segment. The YAP isoform lacking the γ-segment was incapable in binding to SHP2, collectively indicated that YAP requires the leucine-zipper motif, which is encoded in the exon 5 and 7, for the complex formation with SHP2.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2016 2015

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

  • [Journal Article] Dephosphorylated parafibromin is a transcriptional coactivator of the Wnt/Hedgehog/Notch pathways.2016

    • Author(s)
      Kikuchi I, Takahashi-Kanemitsu A, Sakiyama N, Tang C, Tang PJ, Noda S, Nakao K, Kassai H, Sato T, Aiba A, and Hatakeyama M.
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 12887-12887

    • DOI

      10.1038/ncomms12887

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Determination of the catalytic activity of LEOPARD syndrome- associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling2016

    • Author(s)
      Saori Noda, Atsushi Takahashi, Takeru Hayashi, Sei-ichi Tanuma and Masanori Hatakeyama
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 469 Issue: 4 Pages: 1133-1139

    • DOI

      10.1016/j.bbrc.2015.12.117

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Parafibromin転写足場タンパク質機能のリン酸化依存的制御2016

    • Author(s)
      菊地逸平、高橋昌史、畠山昌則
    • Organizer
      第75回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] LEOPARD症候群由来変異型SHP2ホスファターゼのparafibrominに対する触媒活性の同定2016

    • Author(s)
      野田沙織、高橋昌史、林 剛瑠、畠山昌則
    • Organizer
      第75回 日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] LEOPARD症候群特異的変異型SHP2のin vitro脱リン酸化試験による酵素活性解析2016

    • Author(s)
      野田沙織、高橋昌史、林剛瑠、田沼靖一、畠山昌則
    • Organizer
      日本薬学会 第136年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Parafibromin acts as a signaling hub that orchestrates the Wnt, Hedgehog and Notch signaling pathways2015

    • Author(s)
      菊地逸平、高橋昌史、野嶋奈津紀、畠山昌則
    • Organizer
      第74回 日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Book] 実験医学 11月号 発生・器官形成、がん悪性化に関わるHippoシグナル2015

    • Author(s)
      高橋昌史、畠山昌則
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi