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2010 Fiscal Year Final Research Report

Molecular signaling in neuromuscular synaptogenesis, hematopoiesis, and related disorders

Research Project

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Project/Area Number 20247024
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionThe University of Tokyo

Principal Investigator

YAMANASHI Yuji  東京大学, 医科学研究所, 教授 (40202387)

Co-Investigator(Kenkyū-buntansha) HIGUCHI Osamu  東京大学, 医科学研究所, 准教授 (50361720)
MASHIMA Ryuichi  東京大学, 医科学研究所, 助教 (00401365)
Project Period (FY) 2008 – 2010
Keywordsシグナル伝達 / アダプター / タンパク質チロシンキナーゼ
Research Abstract

To understand molecular signaling involved in neuromuscular synaptogenesis, hematopoiesis, and related disorders, we focused on the Dok-family of adaptor proteins. Our findings together revealed that the cytoplasmic protein Dok-7 directly interacts with the receptor tyrosine kinase MuSK and activates it to form neuromuscular synapses. We also revealed that autoantibodies to Lrp4, a MuSK's coreceptor, in patients with myasthenia gravis, and that Dok-1/2/3 suppress histiocytic sarcoma.

  • Research Products

    (15 results)

All 2011 2010 2009 2008 2007 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (1 results) Book (2 results) Remarks (1 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Journal Article] The transcription factor Sp1 plays a crucial role in dok-7 gene expression2011

    • Author(s)
      Hamuro Johko, Yukihiro Hishida, Osamu Higuchi, and Yuji Yamanashi
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 408 Pages: 293-299

    • Peer Reviewed
  • [Journal Article] Autoantibodies to Low-Density Lipoprotein Receptor-Related Protein 4 in Myasthenia Gravis2011

    • Author(s)
      Osamu Higuchi, Hamuro Johko, Masakatsu Motomura, and Yuji Yamanashi
    • Journal Title

      Ann. Neurol

      Volume: 69 Pages: 418-422

    • Peer Reviewed
  • [Journal Article] Mice lacking Dok-1, Dok-2, and Dok-3 succumb to aggressive hisitocytic sarcoma2010

    • Author(s)
      Ryuichi Mashima, Honda Kazuho, Yi Yang, Yohei Morita, Akane Inoue, Sumimasa Arimura, Hiroshi Nishina, Hideo Ema, Hiromitsu Nakauchi, Brian Seed, Hideaki Oda, and Yuji Yamanashi
    • Journal Title

      Lab. Investigation

      Volume: 90 Pages: 1357-1364

    • Peer Reviewed
  • [Journal Article] Dok-7 activates the muscle receptor kinase MuSK and shapes synapse formation2009

    • Author(s)
      Akane Inoue, Kiyoko Setoguchi, Yosuke Matsubara, Kumiko Okada, Nozomi Sato, Yoichiro Iwakura, Osamu Higuchi, and Yuji Yamanashi
    • Journal Title

      Science Signaling

      Volume: 2 Pages: 7

    • Peer Reviewed
  • [Journal Article] The roles of Dok family adaptors in immunoreceptor signaling2009

    • Author(s)
      Ryuichi Mashima, Yukihiro Hishida, Tohru Tezuka, and Yuji Yamanashi
    • Journal Title

      Immunological Reviews

      Volume: 232 Pages: 273-285

    • Peer Reviewed
  • [Journal Article] Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-72008

    • Author(s)
      Johko Hamuro, Osamu Higuchi, Kumiko Okada, Makiko Ueno, Shun-ichiro Iemura, Tohru Natsume, Hayley Spearman, David Beeson, and Yuji Yamanashi
    • Journal Title

      J. Biol. Chem

      Volume: 283 Pages: 5518-5524

    • Peer Reviewed
  • [Journal Article] Dok-1 mediates high-fat diet-induced adipocyte hypertrophy and obesity through modulation of PPARγphosphorylation.2008

    • Author(s)
      Tetsuya Hosooka, Tetsuya Noguchi, Ko Kotani, Takehiro Nakamura, Hiroshi Sakaue, Hiroshi Inoue, Wataru Ogawa, Kazutoshi Tobimatsu, Kazuo Takazawa, Mashito Sakai, Yasushi Matsuki, Ryuji Hiramatsu, Tomoharu Yasuda, Mitchell A
    • Journal Title

      Nature Med

      Volume: 14 Pages: 188-193

    • Peer Reviewed
  • [Journal Article] Dok-7/MuSK signaling and a congenital myasthenic syndrome2008

    • Author(s)
      Yuji Yamanashi, Osamu Higuchi, and David Beeson
    • Journal Title

      Acta Myologica

      Volume: 27 Pages: 25-29

    • Peer Reviewed
  • [Presentation] Plenary Lecture : Dok-7, MuSK, and the development of neuromuscular junction2009

    • Author(s)
      Yuji Yamanashi
    • Organizer
      International Conference on Myasthenia Gravis.(Organized by the EruroMyasthenia Network)
    • Place of Presentation
      Paris
    • Year and Date
      20091201-02
  • [Book] 先天性筋無力症の分子基盤、生体の科学2011

    • Author(s)
      手塚徹、山梨裕司
    • Total Pages
      106-1121
    • Publisher
      医学書院
  • [Book] 受容体型キナーゼの細胞内からの活性、実験医学2009

    • Author(s)
      井上茜、瀬戸口喜代子、樋口理、山梨裕司
    • Total Pages
      1384-1387
    • Publisher
      羊土社
  • [Remarks]

    • URL

      http://www.ims.u-tokyo.ac.jp/genetics/html/home.html

  • [Patent(Industrial Property Rights)] 筋特異的チロシンキナーゼの活性化を制御するポリペプチドをコードするDNA2007

    • Inventor(s)
      山梨裕司, 他
    • Industrial Property Rights Holder
      東京医科歯科大学
    • Industrial Property Number
      特願、2008-520460
    • Filing Date
      2007-04-26
  • [Patent(Industrial Property Rights)] 筋特異的チロシンキナーゼの活性化を制御するポリペプチドをコードするDNA2007

    • Inventor(s)
      山梨裕司, 他
    • Industrial Property Rights Holder
      東京医科歯科大学
    • Industrial Property Number
      US12/329208
    • Filing Date
      2007-12-05
    • Overseas
  • [Patent(Industrial Property Rights)] 筋特異的チロシンキナーゼの活性化を制御するポリペプチドをコードするDNA2007

    • Inventor(s)
      山梨裕司, 他
    • Industrial Property Rights Holder
      東京医科歯科大学
    • Industrial Property Number
      EP07742485. 1
    • Filing Date
      2007-04-26
    • Overseas

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Published: 2013-07-31  

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