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Comprehensive analyses for biological functions and regulatory mechanisms of DOCK family proteins

Research Project

Project/Area Number 25251015
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionKyushu University

Principal Investigator

Fukui Yoshinori  九州大学, 生体防御医学研究所, 教授 (60243961)

Co-Investigator(Kenkyū-buntansha) URUNO Takehito  九州大学, 生体防御医学研究所, 准教授 (80532093)
田中 芳彦  福岡歯科大学, 歯学部, 教授 (00398083)
Project Period (FY) 2013-05-31 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥46,150,000 (Direct Cost: ¥35,500,000、Indirect Cost: ¥10,650,000)
Fiscal Year 2015: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2013: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Keywordsシグナル伝達 / 生体分子 / 癌 / 免疫学 / 遺伝子改変マウス / がん / 免疫 / 低分子量Gタンパク質
Outline of Final Research Achievements

DOCK family proteins are atypical guanine nucleotide exchange factors that mediate GTP-GDP exchange reaction through their DHR-2 domain. Recent evidence indicates that DOCK family proteins are involved in many cellular functions, yet their regulatory mechanisms are poorly understood. In this study, we have analyzed signaling and functions of DOCK family proteins and obtained the following important findings: 1) DOCK5 acts downstream of FCεRI receptor and critically regulates mast cell degranulation. 2) DOCK1 plays a key role in invasion and metastasis of breast cancer cells. 3) The phosphorylation sites of DOCK2 in response to chemokine stimulation were identified. 4) The critical domain required for membrane localization of DOCK8 was identified. 5) The previously unknown function of DOCK8 and its regulatory mechanism were discovered.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (38 results)

All 2016 2015 2014 2013 Other

All Journal Article (19 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 18 results,  Open Access: 3 results) Presentation (18 results) (of which Invited: 5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Parallel regulation of VHL disease by pVHL-mediated degradation of B-Myb and HIF-α.2016

    • Author(s)
      Okumura F, Uematsu K, Byrne S, Hirano M, Joo-Okumura A, Nishikimi A, Shuin T, Fukui Y, Nakatsukasa K, Kamura K.
    • Journal Title

      Mol. Cell. Biol.

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intronic regulation of Aire expression by Jmjd6 for self-tolerance induction in the thymus.2015

    • Author(s)
      Yanagihara T, Sanematsu F, Sato T, Uruno T, Duan X, Tomino T, Harada Y, Watanabe M, Wang Y, Tanaka Y, Nakanishi Y, Suyama M, Yoshinori F.
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 8820-8820

    • DOI

      10.1038/ncomms9820

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dedicator of cytokinesis 2, a novel regulator for smooth muscle phenotypic modulation and vascular remodeling.2015

    • Author(s)
      Guo X, Shi N, Cui X-B, Wang J-N, Fukui Y, Chen S-Y.
    • Journal Title

      Cir. Res.

      Volume: 116 Issue: 10

    • DOI

      10.1161/circresaha.116.305863

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Axl phosphorylates Elmo scraffold proteins to promote Rac activation and cell invasion.2015

    • Author(s)
      Abu-Thuraia A, Gauthier R, Chidiac R, Fukui Y, Screaton RA, Gratton JP, Cote JF.
    • Journal Title

      Mol Cell Biol.

      Volume: 35 Issue: 1 Pages: 76-87

    • DOI

      10.1128/mcb.00764-14

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dedicator of cytokinesis 2, a novel regulator for smooth muscle phenotypic modulation and vascular remodeling.2015

    • Author(s)
      Guo X et al
    • Journal Title

      Cir. Res.

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Thromboxane A2 acts as tonic immunoregulator by preferentialdisruption of low-avidity CD4+ T cell-dendritic cell interactions.2014

    • Author(s)
      Moalli F, Cupovic J, Thelen F, Halbherr P, Fukui Y, Narumiya S, Ludewig B, Stein JV.
    • Journal Title

      J Exp Med.

      Volume: 211 Issue: 13 Pages: 2507-2517

    • DOI

      10.1084/jem.20140137

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neutrophils scan for activated platelets to initiate inflammation.2014

    • Author(s)
      Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I, Nacher M, Pitaval C, Radovanovic I, Fukui Y, McEver RP, Filippi M-D, Lizasoain I, Ruiz-Cabello J, Zarbock A, Moro MA, Hidalgo A.
    • Journal Title

      Science

      Volume: 346 Issue: 6214 Pages: 1234-1238

    • DOI

      10.1126/science.1256478

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DOCK2 is critical for CD8+TCR- graft facilitating cells to enhance engraftment of hematopoietic stem and progenitor cells.2014

    • Author(s)
      Wen Y, Elliott MJ, Huang Y, Miller TO, Corbin DR, Hussain L-R, Ratajczak MZ, Fukui Y, Ildstad ST.
    • Journal Title

      Stem Cells.

      Volume: 32 Issue: 10 Pages: 2732-2743

    • DOI

      10.1002/stem.1780

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils.2014

    • Author(s)
      Damoulakis G, Gambardella L, Rossman K, Lawson C, Anderson K, Fukui Y, Welch H, Der C, Stephens L, Hawkins P.
    • Journal Title

      J Cell Sci.

      Volume: 127 Pages: 2589-2600

    • DOI

      10.1242/jcs.153049

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Rac-specific exchange factors Dock1 and Dock5 are dispensable for the establishment of the glomerular filtration barrier in vivo.2014

    • Author(s)
      Laurin M, Dumouchel A, Fukui Y, Cote J-F.
    • Journal Title

      Small GTPases

      Volume: 4 Issue: 4 Pages: 221-230

    • DOI

      10.4161/sgtp.27430

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 免疫抑制剤開発の新しい分子標的としてのDOCK22014

    • Author(s)
      宇留野武人
    • Journal Title

      実験医学増刊

      Volume: 32 Pages: 184-189

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Annular PIP3 accumulation controls actin architecture and modulates cytotoxicity at the immunological synapse2013

    • Author(s)
      Le Floc'h A, Tanaka Y, Bantilan NS, Voisinne G, Altan-Bonner G, Fukui Y, Huse M.
    • Journal Title

      J Exp Med

      Volume: 210 Issue: 12 Pages: 2721-2737

    • DOI

      10.1084/jem.20131324

    • Related Report
      2013 Annual Research 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 Annual Research 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 Annual Research Report
    • Peer Reviewed
  • [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 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of the microglial protein DOCK2 reduces amyloid burden in a mouse model of Alzheimer's disease.2013

    • Author(s)
      Cimino PJ, Yang Y, Li X, Hemingway JF, Cherne MK, Khademi SB, Fukui Y, Montine KS, Montine TJ, Keene CD
    • Journal Title

      Exp. Mol. Pathol.

      Volume: 94 Issue: 2 Pages: 366-371

    • DOI

      10.1016/j.yexmp.2013.01.002

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rac-specific guanine nucleotide exchange factor DOCK1 is a critical regulator of HER2-mediated breast cancer metastasis2013

    • Author(s)
      Laurin M
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 未定 Issue: 18 Pages: 7434-7439

    • DOI

      10.1073/pnas.1213050110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 1.マスト細胞の脱顆粒反応におけるDOCK5の役割とその制御機構2015

    • Author(s)
      福井宣規
    • Organizer
      第64回日本アレルギー学会学術大会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2015-05-27
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] A novel mechanism controlling Aire protein expression in the thymus.2015

    • Author(s)
      Fukui Y
    • Organizer
      The Fourth BIZAN Immunology Symposium
    • Place of Presentation
      Tokushima, Japan
    • Year and Date
      2015-01-29 – 2015-01-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Critical roles of DOCK family proteins in migration and activation of leukocytes.2015

    • Author(s)
      Fukui Y
    • Organizer
      Keystone Symposium
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2015-01-13 – 2015-01-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The role of DOCK8 in migration and activation of effector CD4+ T cells during immune responses.2014

    • Author(s)
      Harada Y et at.
    • Organizer
      The 43rd Annual Meeting of The Japanese Society for Immunology
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Identification of a novel molecule essential for Aire expression and self-tolerance.2014

    • Author(s)
      Yanagihara T et al
    • Organizer
      The 43rd Annual Meeting of The Japanese Society for Immunology
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] DOCK1 as a novel molecular target for controlling cancer invasion and metastasis.2014

    • Author(s)
      Fukui Y
    • Organizer
      The 25th Annual Meeting of the Japanese Society for Gastroenterolgical Carcinogeniesis
    • Place of Presentation
      福岡
    • Year and Date
      2014-11-13 – 2014-11-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Critical roles of DOCK family proteins in migration and activation of leukocytes.2014

    • Author(s)
      Fukui Y
    • Organizer
      The 24th Hot Spring Harbor International Symposium
    • Place of Presentation
      福岡
    • Year and Date
      2014-11-07 – 2014-11-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Identification of a molecule critical for degranulation of mast cells and anaphylactic reaction2013

    • Author(s)
      Ogawa K et al.
    • Organizer
      Annual Meeting of The Japanese Society for Immunology 2013
    • Place of Presentation
      幕張メッセ,千葉
    • Related Report
      2013 Annual Research Report
  • [Presentation] Critical roles of DOCK2 and DOCK5 in neutrophil chemotaxis, ROS production, and NETs formation2013

    • Author(s)
      Watanabe M et al
    • Organizer
      Annual Meeting of The Japanese Society for Immunology 2013
    • Place of Presentation
      幕張メッセ,千葉
    • Related Report
      2013 Annual Research Report
  • [Presentation] Immune regulatory functions of DOCK family proteins in health and disease2013

    • Author(s)
      Fukui Y
    • Organizer
      Germany-Japan Immunology Seminar
    • Place of Presentation
      日本平ホテル、静岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses2013

    • Author(s)
      Harada Y et al.
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      MICO Milano Congressi、Milan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Critical role of DOCK8 in dendritic cell trafficking during T cell immune responses2013

    • Author(s)
      Shiraishi A et al
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      MICO Milano Congressi、Milan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Critical roles of DOCK2 and DOCK5 in neutrophil chemotaxis, ROS production, and NETs formation2013

    • Author(s)
      Watanabe M et al.
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      MICO Milano Congressi、Milan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Identification of a molecule critical for degranulation of mast cells and anaphylactic reaction2013

    • Author(s)
      Ogawa K et al.
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      MICO Milano Congressi、Milan
    • Related Report
      2013 Annual Research Report
  • [Presentation] B cell-intrinsic role of DOCK2 in T cell-dependent humoral immunity2013

    • Author(s)
      Ushijima M et al.
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      MICO Milano Congressi、Milan
    • Related Report
      2013 Annual Research Report
  • [Presentation] The Rac activator DOCK2 regulates natural killer cell-mediatd cytotoxicity through the lytic synapse formation2013

    • Author(s)
      Yanagihara T et al.
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      MICO Milano Congressi、Milan
    • Related Report
      2013 Annual Research Report
  • [Presentation] DOCK1 as a key molecule for dorsal ruffle formation and cancer cell metastasis

    • Author(s)
      Tajiri H et al.
    • Organizer
      International Symposium between Kyushu U. Post-Global COE and School of Biomedical Sciences, Monash U.
    • Place of Presentation
      Melbourne
    • Related Report
      2013 Annual Research Report
  • [Presentation] Critical role of DOCK8 in dendritic cell trafficking during T cell immune responses

    • Author(s)
      Yamamura K et al
    • Organizer
      International Symposium between Kyushu U. Post-Global COE and School of Biomedical Sciences, Monash U.
    • Place of Presentation
      Melbourne
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] アトピー性皮膚炎モデル非ヒト動物及びその使用2016

    • Inventor(s)
      福井宣規、山村和彦、宇留野武人、古江増隆、
    • Industrial Property Rights Holder
      九州大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-034510
    • Filing Date
      2016-02-25
    • Related Report
      2015 Annual Research Report

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Published: 2013-06-20   Modified: 2019-07-29  

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