ゲノムネットワークプロジェクト

個別生命機能の解析
研究課題 免疫系細胞高次機能を司るDOCK2シグナルネットワークの解明
研究期間 平成18年度〜20年度
研究課題代表者 福井 宣規
所属機関 九州大学生体防御医学研究所
研究目的 免疫系は生体にとって感染に対する必須の防御機構であるが、一方免疫応答したための病態、例えば自己免疫疾患・移植片拒絶は、現代医学が解決すべき問題としてクローズアップされている。本研究はDOCK2のシグナルネットワークを解明することで、これら免疫難病の新しい治療法・予防法開発の>ための分子基盤を提供することを目的とする。
研究概要 受容体刺激から機能発現に至るDOCK2シグナルネットワークの全貌を解明するため、①DOCK2の機能ドメイン及びそれに刺激依存的あるいは恒常的に会合する分子の同定、②DOCK2の新しい機能やその制御機構の解明、③DOCK2の細胞内動態を制御するシグナル伝達系の解明を行う。
研究成果 DOCK2が好中球や形質細胞様樹状細胞において、ケモアトラクタント受容体の下流で機能するRac活性化分子であり、遊走や活性酸素産生に重要な役割を演じることを明らかにすると共に、DOCK2がPIP3と会合し、PI3K依存性に細胞膜に移行することを示した。また、T細胞受容体の下流で誘導されるDOCK2-Racシグナルが、微小管動態を介してIL-4受容体の細胞内輸送とタンパク質分解を制御することで、Th2細胞への分化を抑制しており、この制御機構の破綻がアレルギー疾患の発症につながることを実証した。さらに、縦軸研究とも連携して数10種類に及ぶDOCK2会合分子を同定した。
データ種別 DOCK2シグナルネットワークのポンチ絵
対象生物 マウス
組織・細胞株 CD4+ T細胞
対象遺伝子 DOCK2
実験情報 機能解析、細胞生物学的解析、生化学的解析のまとめ
産出データ
(ダウンロード)
PPI Data
DOCK2シグナルネットワークのポンチ絵(PDF)
XMLデータ -
研究論文・特許出願・
学術発表など
------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:742
PUBLICATION TYPE: journal
PUBLICATION NAME: Nature Immunology
ARTICLE TITLE: T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-09-02
TITLE: T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2
STATUS: Published
AUTHOR NAME: Yoshihiko Tanaka1, Shinjiro Hamano2, Kazuhito Gotoh1, Yuzo Murata3, Yuya Kunisaki1, Akihiko Nishikimi1, Ryosuke Takii1, Makiko Kawaguchi1, Ayumi Inayoshi1, Sadahiko Masuko3, Kunisuke Himeno2, Takehiko Sasazuki4 & Yoshinori Fukui1
AUTHOR AFFILIATION: 1Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, and 2Department of Parasitology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. 3Department of Anatomy and Physiology, Faculty of Medicine, Saga University, Saga 849-8501, Japan. 4International Medical Center of Japan, Tokyo 162-8655, Japan

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1185
PUBLICATION TYPE: journal
PUBLICATION NAME: Journal of Cell Biology
ARTICLE TITLE: DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-12-14
TITLE: DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis
STATUS: Published
AUTHOR NAME: Yuya Kunisaki,1 Akihiko Nishikimi,1 Yoshihiko Tanaka,1 Ryosuke Takii,1 Mayuko Noda,1,2 Ayumi Inayoshi,1,2 Ken-ichi Watanabe,3 Fumiyuki Sanematsu,1 Takehiko Sasazuki,4 Takehiko Sasaki,2,3 and Yoshinori Fukui1,2
AUTHOR AFFILIATION: 1Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan 2PRESTO, Japan Science and Technology Agency, Saitama 332-0012, Japan 3Division of Microbiology, Department of Pathology and Immunology, Akita University School of Medicine, Akita 010-8543, Japan 4International Medical Center of Japan, Tokyo 162-8655, Japan

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1186
PUBLICATION TYPE: journal
PUBLICATION NAME: Blood
ARTICLE TITLE: Differential requirement for DOCK2 in migration of plasmacytoid DCs versus myeloid DCs
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-03-15
TITLE: Differential requirement for DOCK2 in migration of plasmacytoid DCs versus myeloid DCs
STATUS: Published
AUTHOR NAME: Kazuhito Gotoh, 1,2 Yoshihiko Tanaka, 1 Akihiko Nishikimi, 1 Ayumi Inayoshi, 1 Munechika Enjoji, 2 Ryoichi Takayanagi, 2 Takehiko Sasazuki, 3 and Yoshinori Fukui1
AUTHOR AFFILIATION: 1Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; 2Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 3International Medical Center of Japan, Tokyo, Japan.

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1187
PUBLICATION TYPE: Conference
PUBLICATION NAME: 18th Forum in Dojin
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-12-14
TITLE: 免疫系細胞高次機能を司るCDMファミリー分子DOCK2
STATUS: Presented
AUTHOR NAME: 福井宣規
AUTHOR AFFILIATION: 九州大学生体防御医学研究所

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1398
PUBLICATION TYPE: journal
PUBLICATION NAME: Biochem Biophys Res Commun.
ARTICLE TITLE: Dock2 participates in bone marrow lympho-hematopoiesis
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-02-29
TITLE: Dock2 participates in bone marrow lympho-hematopoiesis
STATUS: Published
AUTHOR NAME: Kikuchi T, Kubonishi S, Shibakura M, Namba N, Matsui T, Fukui Y, Tanimoto M, Katayama Y.
AUTHOR AFFILIATION: Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Cho-ku, Kobe 650-0017, Japan Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1399
PUBLICATION TYPE: journal
PUBLICATION NAME: Journal of Experimental Medicine
ARTICLE TITLE: A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-03-15
TITLE: A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress
STATUS: Published
AUTHOR NAME: Nombela-Arrieta C, Mempel TR, Soriano SF, Mazo I, Wymann MP, Hirsch E, Martínez-A C, Fukui Y, von Andrian UH, Stein JV.
AUTHOR AFFILIATION: 1 Theodor Kocher Institute, University of Bern, CH-3012 Bern, Switzerland 2 The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, MA 02115 3 Department of Clinical Biological Sciences, Institute of Biochemistry and Genetics, University of Basel, CH-4003 Basel, Switzerland 4 Department of Genetics, Biology and Biochemistry, University of Turin, 10060 Turin, Italy 5 Department of Immunology and Oncology, National Center for Biotechnology-CSIC, 28049 Madrid, Spain 6 PRESTO, Japan Science and Technology Agency, and Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1400
PUBLICATION TYPE: journal
PUBLICATION NAME: Journal of Immunology
ARTICLE TITLE: DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin alpha4beta1
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2006-10-15
TITLE: DOCK2 is required for chemokine-promoted human T lymphocyte adhesion under shear stress mediated by the integrin alpha4beta1
STATUS: Published
AUTHOR NAME: García-Bernal D, Sotillo-Mallo E, Nombela-Arrieta C, Samaniego R, Fukui Y, Stein JV, Teixidó J.
AUTHOR AFFILIATION: * Department of Immunology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain; {dagger} Theodor Kocher Institute, University of Bern, Bern, Switzerland; {ddagger} Unidad de Microscopía Confocal, Hospital Universitario Gregorio Marañón, Madrid, Spain; and § Department of Immunobiology, Division of Immunogenetics, and Neuroscience Medical Institute of. Bioregulation, Kyushu University, Japan

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1402
PUBLICATION TYPE: journal
PUBLICATION NAME: Blood
ARTICLE TITLE: DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2006-10-01
TITLE: DOCK2 regulates chemokine-triggered lateral lymphocyte motility but not transendothelial migration.
STATUS: Published
AUTHOR NAME: Shulman Z, Pasvolsky R, Woolf E, Grabovsky V, Feigelson SW, Erez N, Fukui Y, Alon R.
AUTHOR AFFILIATION: From the Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; and Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitoma, Japan.

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1405
PUBLICATION TYPE: journal
PUBLICATION NAME: Nature Cell Biology
ARTICLE TITLE: Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery.
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2007-01-07
TITLE: Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery.
STATUS: Published
AUTHOR NAME: Handa Y, Suzuki M, Ohya K, Iwai H, Ishijima N, Koleske AJ, Fukui Y, Sasakawa C.
AUTHOR AFFILIATION: 1. Department of Microbiology and Immunology, Institute of Medical Science and University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. 2. Department of Infectious Control, International Research Center for Infectious Diseases, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. 3. Department of Molecular Biophysics and Biochemistry, Department of Neurobiology, and Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06520, USA. 4. Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan. 5. CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.

------------------------------ PUBLICATION ------------------------------
PUBLICATION ID:1406
PUBLICATION TYPE: Conference
PUBLICATION NAME: 第4回ゲノムネットワークプロジェクト公開シンポジウム
ARTICLE TITLE:
SUBMIT DATE:
ACCEPT DATE:
PUBLICATION DATE: 2008-02-19
TITLE: 免疫系細胞高次機能を司るDOCK2シグナルネットワーク
STATUS: Presented
AUTHOR NAME: 福井宣規
AUTHOR AFFILIATION: 九大生医研免疫遺伝学分野

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