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Role of DOCK2 in antigen-specific humoral immunity

Research Project

Project/Area Number 24590586
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Immunology
Research InstitutionKitasato University (2013-2015)
Kyushu University (2012)

Principal Investigator

Nishikimi Akihiko  北里大学, 理学部, 准教授 (70404019)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
KeywordsB細胞 / 抗原応答 / シグナル伝達 / 抗体産生 / Rac / 細胞遊走 / 免疫応答 / 分化 / 細胞骨格 / 免疫シナプス / キナーゼ
Outline of Final Research Achievements

The small G protein Rac is known to play important roles in B cell activation by acting downstream of B cell receptor (BCR). We found that DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells, is essential for BCR-mediated Rac activation.DOCK2-deficient B cells failed to form immunological synapse and displayed impaired antigen-stimulated growth in vitro. DOCK2 knock-out mice were shown to have impaired production of antibody in response to antigen immunization, indicating DOCK2 plays a critical role in humoral immunity.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2016 2015 2014 2013 2012

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (5 results)

  • [Journal Article] Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis.2015

    • Author(s)
      Ishihara S, Nishikimi A, Umemoto E, Miyasaka M, Saegusa M, Katagiri K
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 8982-8982

    • DOI

      10.1038/ncomms9982

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation.2014

    • Author(s)
      Watanabe M, Terasawa M, Miyano K, Yanagihara T, Uruno T, Sanematsu F, Nishikimi A, Cote JF, Sumimoto H, Fukui Y.
    • Journal Title

      J Immunol.

      Volume: 193 Issue: 11 Pages: 5660-5667

    • DOI

      10.4049/jimmunol.1400885

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the cell surface for lymphocyte trafficking.2014

    • Author(s)
      Nishikimi A, Ishihara S, Ozawa M, Etoh K, Fukuda M, Kinashi T and Katagiri K
    • Journal Title

      Sci. Signal.

      Volume: Vol. 7, Issue 336 Issue: 336

    • DOI

      10.1126/scisignal.2005199

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation.2014

    • Author(s)
      Ogawa K, Tanaka Y, Uruno T, Duan X, Harada Y, et al.
    • Journal Title

      J. Exp. Med.

      Volume: (In press) Issue: 7 Pages: 1407-1419

    • DOI

      10.1084/jem.20131926

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation2013

    • Author(s)
      Sakai Y, Tanaka Y, Yanagihara T, Watanabe M, Duan X, Terasawa M, Nishikimi A, Sanematsu F, Fukui Y.
    • Journal Title

      Blood

      Volume: 122 Issue: 3 Pages: 386-393

    • DOI

      10.1182/blood-2012-12-475897

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The cell polarity protein mInsc regulates neutrophil chemotaxis via a noncanonical G protein signaling pathway2013

    • Author(s)
      Kamakura S., Nomura M., Hayase J., Iwakiri Y., Nishikimi A., Fukui Y., Takayanagi R., Sumimoto H.
    • Journal Title

      Dev Cell

      Volume: 26 Issue: 3 Pages: 292-302

    • DOI

      10.1016/j.devcel.2013.06.008

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immune regulatory functions of DOCK family proteins in health and disease2013

    • Author(s)
      Nishikimi A et al.
    • Journal Title

      Exp. Cell. Res.

      Volume: 319 Issue: 15 Pages: 2343-2349

    • DOI

      10.1016/j.yexcr.2013.07.024

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phosphatidic acid-dependent recruitment and function of the Rac activator DOCK1 during dorsal ruffle formation.2013

    • Author(s)
      Sanematsu F, Nishikimi A, Watanabe M, Hongu T, Tanaka Y, Kanaho Y, Cote JF, Fukui Y
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 12 Pages: 8092-8100

    • DOI

      10.1074/jbc.m112.410423

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Next-generation sequencing coupled with a cell-free display technology for high-throughput production of reliable interactome data2012

    • Author(s)
      Fujimori S
    • Journal Title

      Scientific Reports

      Volume: 2 Issue: 1 Pages: 1-5

    • DOI

      10.1038/srep00691

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration2012

    • Author(s)
      Terasawa M, Uruno T, Mori S, Kukimoto-Niino M, Nishikimi A, Sanematsu F, Tanaka Y, Yokoyama S, Fukui Y
    • Journal Title

      PLoS ONE

      Volume: 7 Issue: 9 Pages: e46277-e46277

    • DOI

      10.1371/journal.pone.0046277

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migrataon during immune responses2012

    • Author(s)
      Yosuke Harada, Yoshihiko Tanaka, Masao Terasawa, Markus Pieczyk, Katsuyoshi Habiro, Tomoya Katakai, Kyoko Hanawa-Suetsugu, Mutsuko Kukimoto-Niino, Tomoko Nishizaki, Mikako Shirouzu, Xuefeng Duan, Takehito Uruno, Akihiko Nishikimi, Fumiyuki Sanematsu, Shigeyuki Yokoyama, Jens V.Stein, Tatsuo Kinashi, Yoshinori Fukui
    • Journal Title

      Blood

      Volume: (In press) Issue: 19 Pages: 4451-4461

    • DOI

      10.1182/blood-2012-01-407098

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activatorDOCK22012

    • Author(s)
      Nishikimi A, Uruno T, Duan X, Cao Q, Okamura Y, Saitoh T, Saitoh N, Sakaoka S, Du Y, Suenaga A, Kukimoto-Niino M, Miyano K, Gotoh K, Okabe T, Sanematsu F, Tanaka Y, Sumimoto H., Honma T, Yokoyama S, Nagano T, Kohda D, Kanai M, and Fukui Y
    • Journal Title

      Chem. Biol

      Volume: 19 Issue: 4 Pages: 488-497

    • DOI

      10.1016/j.chembiol.2012.03.008

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Rap1とfilaminの相互作用を介したリンパ球の接着制御2016

    • Author(s)
      錦見昭彦,石原沙耶花,片桐晃子
    • Organizer
      生体運動合同班会議2016
    • Place of Presentation
      キャンパスプラザ京都(京都府京都市)
    • Year and Date
      2016-01-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Rab13 is a downstream effector of Mst1 to mediate LFA-1 activation crucial for lymphocyte trafficking.2015

    • Author(s)
      Nishikimi A, Ishiahra S, Katagiri K
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Lymphocyte arrest was induced by the binding of active Rap1 to filamins.2015

    • Author(s)
      Ishiahra S, Nishikimi A, Katagiri K
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Rab13 is a downstream effector of Mst1 to mediate LFA-1 activation crucial for lymphocyte trafficking.2014

    • Author(s)
      Nishikimi A, Ishihara S, Ozawa M, Kinashi T, Katagiri K.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10
    • Related Report
      2014 Research-status Report
  • [Presentation] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses.2013

    • Author(s)
      Nishikimi, A., Harada, Y., Tanaka, Y., Terasawa, M., Stein, J.V., Kinashi, T., Fukui, Y.
    • Organizer
      The 23rd CDB Meeting Building Multicellular Systems from Cellular Cross-Talk
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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