Molecular mechanism of lymphocyte activation by a novel CDM-family protein.

• Project/Area Number: 21590537
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyushu University
• Principal Investigator: TANAKA Yoshihiko 九州大学, 生体防御医学研究所, 准教授 (00398083)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 免疫学 / シグナル伝達 / 細胞・組織 / 発生・分化 / 脳神経疾患 / 細胞/組織 / 発生/分化 / 細胞 / 組織 / 発生 / 分化

Research Abstract

A novel CDM庸amily protein was studied for molecular mechanism of lymphocyte activation and guanine nucleotide exchange factors. The numbers of T cells in the spleen and the peripheral lymph nodes were reduced in the gene妖eficient mice. Also, antigen耀pecific T幼ell proliferation was impaired in the gene妖eficient mice. Finally, the novel CDM庸amily protein functioned as a Cdc42耀pecific guanine nucleotide exchange factor.

Research Products

• [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses (2012)
  • Author(s): Harada Y., Tanaka Y.(equal contributor(co-first author)), Terasawa M., Pieczyk M., Habiro K., Katakai T., HanawaSuetsugu K., Kukimoto-Niino M., Nishizaki T., Shirouzu M., Duan X., Uru no T., Nishikimi A., Sanematsu F., Yokoyama S., Stein J. V., Kinashi T.
  • Journal Title: Blood Volume: 119 Pages: 4451-4461
  • Peer Reviewed
• [Journal Article] Blockade of inflammatory responses by a small molecule inhibitor of the Rae activator DOCK2 (2012)
  • Author(s): Nishikimi A., Uru no T., Duan X., Cao Q., Okumura Y., Saitoh T., Saito N., Sakaoka S., Du Y., Suenaga A., Kukimoto-Ni ine M., Miyano K., Gotoh K., Okabe T., Sanematsu F., Tanaka Y., Sumimoto H., Honma T., Yokoyama S., Nagano T., Kohda D., Kanai M., Fukui
  • Journal Title: Chem. Biol Volume: 19 Pages: 448-497
  • Peer Reviewed
• [Journal Article] DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses (2012)
  • Author(s): Harada Y., et al
  • Journal Title: Blood Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2 (2012)
  • Author(s): Nishikimi A., et al
  • Journal Title: Chem.Biol. Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): 田中芳彦, 他
  • Journal Title: 臨床免疫・アレルギー科 Volume: 56 Pages: 728-735
• [Journal Article] 自然免疫システムにおけるDOCK2の機能とその制御 (2011)
  • Author(s): 田中芳彦, 他
  • Journal Title: 細胞工学 Volume: 56 Pages: 728-735
  • NAID: 40018807879
• [Journal Article] Selective control of type I IFN induction by the Rae activator DOCK2 during TLRmediated plasmacytoid dendritic cell activation (2010)
  • Author(s): Gotoh K., Tanaka Y.(equal contributor(co-first author)), Nishikimi A., Nakamura R., Yamada H., Maeda N., Ishikawa T., Hoshino K., Uru no T., Cao Q., Higashi S., Kawaguchi Y., Enjoji M., Takayanagi R., Kaisho T., Yoshikai Y., Fukui Y.
  • Journal Title: J. Exp. Med Volume: 207 Pages: 721-730
  • Peer Reviewed
• [Journal Article] DOCKl8o is a Rae activator that regulates cardiovascular development by acting downstream of CXCR4 (2010)
  • Author(s): Sanematsu F., Hirashima M., Laurin M., Takii R., Nishikimi A., Kitajima K., Ding G., Neda M., Murata Y., Tanaka Y., Masuko S., Suda T., Meno C., Cote J. F., Nagasawa T., Fukui Y.
  • Journal Title: Circ. Res Volume: 107 Pages: 1102-1105
  • Peer Reviewed
• [Journal Article] Selective control of type I IFN induction by the Rac activator DOCK 2 during TLR-mediated plasmacytoid dendritic cell activation. (2010)
  • Author(s): Gotoh K., et al.
  • Journal Title: J.Exp.Med. Volume: 207 Pages: 721-730
  • Peer Reviewed
• [Journal Article] DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4. (2010)
  • Author(s): Sanematsu F., et al.
  • Journal Title: Circ.Res. Volume: 107 Pages: 1102-1105
  • Peer Reviewed
• [Journal Article] Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation (2010)
  • Author(s): Gotoh K., et al.
  • Journal Title: J.Exp.Med. (印刷中)
  • Peer Reviewed
• [Journal Article] Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotax i s (2009)
  • Author(s): Nishikimi A., Fukuhara H., Sn W., Hongu T., Takasuga S., Mihara H., Cao Q., Sanematsu F., Kanai M., Hasegawa H., Tanaka Y., Shibasaki M., Kanaho Y., Sasaki T., Frohman M. A., Fukui Y.
  • Journal Title: Science Volume: 324 Pages: 384-387
  • Peer Reviewed
• [Journal Article] CCL2l mediates CD4+ T cell costimulationviaa DOCK2/Racdependent pathway (2009)
  • Author(s): Gollmer K., AspertiBoursin F., Tanaka Y., Okkenhaug K., Vanhaesebroeck B., Peterson J. R., Fukui Y., Donnadieu E., Stein J. V.
  • Journal Title: Blood Volume: 114 Pages: 580-558
  • Peer Reviewed
• [Journal Article] Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis (2009)
  • Author(s): Nishikimi A., et al.
  • Journal Title: Science 324 Pages: 384-387
  • Peer Reviewed
• [Journal Article] CCL21 mediates CD4^+ T cell costimulation via a DOCK2/Rac-dependent pathway (2009)
  • Author(s): Gollmer K., et al.
  • Journal Title: Blood 114 Pages: 580-588
  • Peer Reviewed
• [Presentation] Identification of a signaling molecule critical for dendritic cell migration in three-dimensional environments (2012)
  • Author(s): Harada Y., et al
  • Organizer: 9^<th> Global-COE international symposium and 8^<th> young investigators forum
  • Place of Presentation: Fukuoka
  • Year and Date: 2012-01-21
• [Presentation] Identification of a signaling molecule critical for dendritic cell migration in threedimensional environments (2012)
  • Author(s): Harada Y., Tanaka, Y. Terasawa M., and Fukui, Y.
  • Organizer: The 9th Global COE International Symposium and 8th young investigators forumhe 9th Global COE International Symposium and 8th young investigators forum
  • Place of Presentation: 福岡
• [Presentation] Identification of a signaling molecule critical for dendritic cell migration in threedimensional environments (2012)
  • Author(s): Harada Y., Tanaka, Y. Terasawa M., and Fukui, Y.
  • Organizer: The 10th Global COE International Symposium and 7th young investigators forum
  • Place of Presentation: 京都
• [Presentation] Regulation of FcεRI-mediated mast cell degranulation by the atypical GEF (2011)
  • Author(s): Ogawa K., et al
  • Organizer: 10^<th> Global-COE international symposium and 7^<th> young investigators forum
  • Place of Presentation: Singapore
  • Year and Date: 2011-12-23
• [Presentation] Regulation of NK cell-mediated cytotoxicity by the atypical Rac activators (2011)
  • Author(s): Sakai Y., et al
  • Organizer: 10^<th> Global-COE international symposium and 7^<th> young investigators forum
  • Place of Presentation: Singapore
  • Year and Date: 2011-12-23
• [Presentation] Identification of a signaling molecule critical for dendritic cell migration in three-dimensional environments (2011)
  • Author(s): Harada Y., et al
  • Organizer: 10^<th> Global-COE international symposium and 7^<th> young investigators forum
  • Place of Presentation: Singapore
  • Year and Date: 2011-12-23
• [Presentation] 免疫系特異的なRac活性化因子DOCK2を標的とした免疫抑制剤の開発 (2011)
  • Author(s): 錦見昭彦, 他
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2011-11-27
• [Presentation] The atypical Rac activator DOCK5 regulates osteoclast function for bone homeostasis. (2011)
  • Author(s): Sakai Y., et al.
  • Organizer: 7^<th> Global-COE international symposium and 6^<th> young investigators forum
  • Place of Presentation: Angsana Resort & Spa Bintan(Indonesia)
  • Year and Date: 2011-02-12
• [Presentation] Regulation of FceRImediated mast cell de granulation by the atypical GEF (2011)
  • Author(s): Ogawa K., Tanaka Y., Terasawa M., Duan X., Sanematsu F., and Fukui Y.
  • Organizer: The 10th Global COE International Symposium and 7th young investigators forum'
  • Place of Presentation: 京都
• [Presentation] Regulation of NK cellmediated cytotoxicity by the atypical Rae activators (2011)
  • Author(s): Sakai Y., Tanaka Y., and Fukui Y.
  • Organizer: The 10th Global COE International Symposium and 7th young investigators forum
  • Place of Presentation: 京都
• [Presentation] 免疫系特異的なRae活性化因子DOCK2を標的とした免疫抑制剤の開発 (2011)
  • Author(s): 錦見昭彦、田中芳彦、福井宣規
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 千葉
• [Presentation] Critical role of DOCK2 in type I IFN induction in plasmacytoid dendritic cells. (2010)
  • Author(s): Gohoh K., et al.
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸国際展示場(兵庫県)
  • Year and Date: 2010-08-23
• [Presentation] Critical role of DOCK2 in type I IFN induction in plasmacytoid dendritic cells. (2010)
  • Author(s): Gohoh K., et al.
  • Organizer: 5^<th> International Symposium of Institute Network
  • Place of Presentation: KKR金沢(石川県)
  • Year and Date: 2010-06-24
• [Presentation] TLRを介した形質細胞様樹状細胞活性化におけるDOCK2の役割 (2010)
  • Author(s): 後藤和人, 他
  • Organizer: Kyoto T Cell Conference
  • Place of Presentation: 京都大学(京都府)
  • Year and Date: 2010-06-04
• [Presentation] 形質細胞様樹状細胞によるI型インターフェロン産生におけるDOCK2の役割 (2009)
  • Author(s): 後藤和人, 他
  • Organizer: 第39回日本免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] 免疫応答を司る免疫系受容体のメンブレントラフィックを介した時間的空間的制御 (2009)
  • Author(s): 田中芳彦, 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] The atypicalRaec activatorDOCKss regulates osteoclast function for bone homeostasis (2009)
  • Author(s): Sakai Y., Tanaka Y., and Fukui Y.
  • Organizer: The 7th Global COE International Symposium and 6th young investigators forum
  • Place of Presentation: 京都
• [Presentation] Critical role of DOCK2 in type I IFN induction in plasmacytoid dendritic cells (2009)
  • Author(s): Gotoh K., Tanaka Y., Nishikimi A., Nakamura R., Yamada H., Hoshino K., Kaisho T., Yoshikai Y., and Fukui Y.
  • Organizer: The 14th international congress of immunology
  • Place of Presentation: 神戸
• [Presentation] Critical Role of DOCK2 in Type I IFI￥Induction in Plasmacytoid Dendritic cells (2009)
  • Author(s): Gotoh K., Tanaka Y., Nishikimi A., Nakamura R., Yamada H., Higashi S., Uru no T., Yoshikai Y., and Fukui Y.
  • Organizer: The 5th International Symposiun of Institute Network'
  • Place of Presentation: 金沢
• [Presentation] TLRを介した形質細胞様樹状細胞活性化におけるDOCK2の役割 (2009)
  • Author(s): 後藤和人、田中芳彦. 、福井宣規
  • Organizer: 第20回Kyoto T Cell Conference
  • Place of Presentation: 京都
• [Presentation] Critical role of DOCK2 in Type I IFN induction in plasmacytoid dendritic cells (2009)
  • Author(s): Gotoh K., Tanaka Y., and Fukui Y.
  • Organizer: The 5th Global COE International Symposium
  • Place of Presentation: 京都
• [Presentation] 形質細胞様樹状細胞による1型インターフェロン産生におけるDOCK2の役割 (2009)
  • Author(s): 後藤和人、田中芳彦、錦見昭彦、吉開泰信、福井宣規
  • Organizer: 第39回日本免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] 免疫応答を司る免疫系受容体のメンブレントラフィックを介した時間的空間的制御 (2009)
  • Author(s): 田中芳彦、福井宣規
  • Organizer: 第82回日本生化学会大会(シンポジウム)
  • Place of Presentation: 神戸
• [Book] 形質細胞様樹状細胞におけるDOCK2を介した1型インターフェロン産生の制御機構.臨床免疫 (2011)
  • Author(s): 田中芳彦, 福井宣規
  • Publisher: アレルギー科
• [Book] 自然免疫システムにおけるDOCK2の機能とその制御 (2011)
  • Author(s): 田中芳彦, 福井宣規
  • Publisher: 細胞工学
• [Remarks]
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• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/iden/
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  • URL: http://www.bioreg.kyushu-u.ac.jp/iden/