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Analysis of the conformational transitions and functional modifications in membrane proteins

Planned Research

Project AreaIntegrative understanding of biological processes mediated by transient macromolecular complexes; New technology for visualizing physiologically metastable states.
Project/Area Number 21121007
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionOsaka University

Principal Investigator

HAYASAKA Haruko  大阪大学, 医学(系)研究科(研究院), 助教 (70379246)

Co-Investigator(Kenkyū-buntansha) BAI Zongbin  大阪大学, 免疫学フロンティア研究センター, 特任助教 (10512840)
Co-Investigator(Renkei-kenkyūsha) MIYASAKA Masayuki  大阪大学, 医学系研究科, 教授 (50064613)
Project Period (FY) 2009-07-23 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥101,530,000 (Direct Cost: ¥78,100,000、Indirect Cost: ¥23,430,000)
Fiscal Year 2013: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
Fiscal Year 2012: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
Fiscal Year 2011: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2010: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
Fiscal Year 2009: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Keywordsケモカイン / 細胞運動 / 接着分子 / GPCR / 細胞遊走 / 細胞移動 / 免疫細胞 / ケモカインシグナル / がん転移 / 膜ラッフル / リンパ節転移 / 乳癌 / リンパ節 / 癌転移
Research Abstract

In various cancer cells, the expression of adhesion molecules and chemokine receptor shows a positive correlation with the metastatic potential, suggesting a possible involvement of those molecules in cancer metastasis. CD44 plays a role in cell adhesion by binding to its ligand hyaluronate. Chemokines are critical regulators of cell migration in the context of effective and appropriate immune responses, inflammation, angiogenesis and tumor progression. In this research project, we found that the transition of CD44 molecular structure by ligand binding is possibly involved in the CD44-mediated tumor progression. We also found that the dynamics of chemokine receptor localization on the plasma membrane are important for their function in cell migration.

Report

(6 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • 2009 Annual Research Report

Research Products

(34 results)

All 2013 2012 2011 2010 2009 Other

All Journal Article (19 results) (of which Peer Reviewed: 6 results) Presentation (14 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] Dynamic changes in endothelial cell adhesion molecule nepmucin/CD300LG expression under physiological and pathological conditions2013

    • Author(s)
      Umemoto, E., Takeda, A., Jin, S., Luo, Z., Nakahogi, N., Hayasaka, H., Lee, CM., Tanaka, T., and Miyasaka, M
    • Journal Title

      PLoS ONE

      Volume: 8

    • Related Report
      2013 Final Research Report
  • [Journal Article] FAK-related nonkinase is a multifunctional negative regulator of pulmonary fibrosis2013

    • Author(s)
      Ding, Q., Cai, G-Q., Hu, M., Yang, Y., Zheng, A., Tang, Q., Gladson, CL., Hayasaka, H.,Wu, H., You, Z., Southern, BD., Grove, LM., Rahaman, SO., Fang,H., and Olman, MA
    • Journal Title

      Am. J. Pathol

      Volume: 182 Pages: 1572-1584

    • Related Report
      2013 Final Research Report
  • [Journal Article] Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis2013

    • Author(s)
      Bai, Z., Cai, L., Umemoto, E., Takeda, A., Tohya, K., Komai, Y., Veeraveedu, PT., Hata, E., Sugiura, Y., Kubo, A., Suematsu, M., Hayasaka, H., Okudaira, S., Aoki, J., Tanaka T., Albers, HMHG., Ovaa, H., and Miyasaka, M
    • Journal Title

      J. Immunol

      Volume: 190 Pages: 2036-2048

    • Related Report
      2013 Final Research Report
  • [Journal Article] Dynamic changes in endothelial cell adhesion molecule nepmucin/CD300LG expression under physiological and pathological conditions.2013

    • Author(s)
      Umemoto, E, Takeda, A., Jin, S., Luo, Z., Nakahogi, N., Hayasaka, H., Lee, C.M., Tanaka, T. & Miyasaka, M.
    • Journal Title

      PLOS One

      Volume: 8 Pages: 1-12

    • DOI

      10.1371/journal.pone.0083681

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 小林 大地, 宮坂 昌之, 早坂 晴子2013

    • Author(s)
      ケモカイン受容体の協働作用による効率的なリンパ球移動の誘導
    • Journal Title

      生体の科学

      Volume: 694 Pages: 398-399

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis2013

    • Author(s)
      Bai Z
    • Journal Title

      J Immunol.

      Volume: 190 Pages: 2036-2048

    • DOI

      10.4049/jimmunol.1202025

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Constitutive plasmacytoid dendritic cell migration to the splenic white pulp is cooperatively regulated by CCR7- and CXCR4-mediated signaling2012

    • Author(s)
      Umemoto, E., Otani, K Ikeno, T., Verjan Garcia N, Hayasaka, H., Bai, Z., Jang MH., Tanaka T., Ueda, K., and Miyasaka, M
    • Journal Title

      J. Immunol

      Volume: 189 Pages: 191-199

    • Related Report
      2013 Final Research Report
  • [Journal Article] Constitutive Plasmacytoid Dendritic Cell Migration to the Splenic White Pulp Is Cooperatively Regulated by CCR7- and CXCR4-Mediated Signaling.2012

    • Author(s)
      Umemoto, E.
    • Journal Title

      Journal of Immunology

      Volume: 189 Pages: 191-199

    • DOI

      10.4049/jimmunol.1200802

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel regulators of lymphocyte trafficking across high endothelial venules2011

    • Author(s)
      Umemoto, E., Hayasaka, H., Bai, Z., Cai, L., Yonekura, S., Peng, X., Takeda, A., Tohya, K., Miyasaka, M
    • Journal Title

      Crit. Rev. Immunol

      Volume: 31 Pages: 147-169

    • Related Report
      2013 Final Research Report
  • [Journal Article] Novel regulators of lymphocyte trafficking across high endothelial venules2011

    • Author(s)
      Umemoto E, Hayasaka H Bai Z, Cai L.Yonekura S, Peng X, Takeda A, Tohya K, Miyasaka M
    • Journal Title

      Crit.Rev.Immunol

      Volume: 31 Pages: 147-169

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌の進展、転移に関与するリンフォイドケモカイン2011

    • Author(s)
      早坂晴子、宮坂昌之
    • Journal Title

      実験医学増刊

      Volume: 29 Pages: 119-124

    • Related Report
      2011 Annual Research Report
  • [Journal Article] リンパ球トラフィキングをつかさどる新しい分子機構-生理活性脂質産生酵素オートタキシンとその産物リゾフォスファチジン酸の役割2011

    • Author(s)
      白忠彬、蔡林君、梅本英司、池野嵩、秦枝里奈、早坂晴子、宮坂昌之
    • Journal Title

      炎症と免疫別冊

      Volume: 19 Pages: 8-13

    • Related Report
      2011 Annual Research Report
  • [Journal Article] ケモカインによる白血球、癌細胞の生体内移動調節とケモカイン共働作用の関与2011

    • Author(s)
      早坂晴子、岡田麻里、白忠彬、黒田康嵩、吉田淳一、宮坂昌之
    • Journal Title

      生化学

      Volume: 83 Pages: 930-937

    • NAID

      10029850204

    • Related Report
      2011 Annual Research Report
  • [Journal Article] がんとリンフォイドケモカイン2011

    • Author(s)
      黒田康嵩、宮坂昌之、早坂晴子、
    • Journal Title

      侵襲と免疫

      Volume: 20 Pages: 38-39

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Neogenesis and development of the high endothelial venules that mediate lymphocyte trafficking2010

    • Author(s)
      Hayasaka, H., Taniguchi, K., Fukai, S. and Miyasaka, M
    • Journal Title

      Cancer Sci

      Volume: 101 Pages: 2302-2308

    • NAID

      10027833068

    • Related Report
      2013 Final Research Report
  • [Journal Article] Two-state conformations in the hyaluronan-binding domain regulate CD44 adhesiveness under flow condition2010

    • Author(s)
      Ogino, S., Nishida, N., Umemoto, R., Suzuki, M., Takeda, M., Terasawa, H., Kitayama, J., Matsumoto, M., Hayasaka, H., Miyasaka, M., and Shimada, I
    • Journal Title

      Structure

      Volume: 18 Pages: 649-656

    • Related Report
      2013 Final Research Report 2010 Annual Research Report
  • [Journal Article] Neogenesis and development of the high endothelial venules that mediate lymphocyte trafficking2010

    • Author(s)
      Hayasaka H
    • Journal Title

      Cancer Science

      Volume: 101 Pages: 2302-2308

    • NAID

      10027833068

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CXCL12 promotes CCR7-dependent naïve T cell trafficking to lymph nodes and Peyer's patches2009

    • Author(s)
      Bai, Z, Hayasaka, H (co-first authors), Kobayashi, M, Li,W, Guo, Z, Jang, MH, Kondo, A, Choi, BI, Iwakura, Y, and Miyasaka, M
    • Journal Title

      J. Immunol

      Volume: 182 Pages: 1287-1295

    • Related Report
      2013 Final Research Report
  • [Journal Article] CXCL12 promotes CCR7-dependent naive T cell trafficking to lymphnodes and Peyer's patches.2009

    • Author(s)
      Bai Zhongbin, Haruko Hayasaka, et.al
    • Journal Title

      Journal of Immunology VOL.182

      Pages: 1287-1295

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chemokine receptor oligomerization : a potential mechanism for regulating lymphocyte and cancer cell migration2013

    • Author(s)
      Haruko Hayasaka, Daichi Kobayashi, Masayuki Miyasaka
    • Organizer
      第51回日本生物物理学会シンポジウム
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2013-10-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 乳癌リンパ節転移におけるケモカイン受容体CXCRおよびCCR7の協働作用2012

    • Author(s)
      早坂 晴子
    • Organizer
      日本癌学会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-19
    • Related Report
      2012 Annual Research Report
  • [Presentation] The HIV-1 gp120/CXCR4 interaction promotes CCR7-dependent CD4 T cell trafficking into lymph nodes2012

    • Author(s)
      Hayasaka H, Yoshimura H, Kobayashi D.Nakayama EE, Shioda T.Bai Z, Miyasaka M
    • Organizer
      Keystone Symposium
    • Place of Presentation
      Beaver Run Resort, Brick enridge, Colorado (USA)
    • Year and Date
      2012-01-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] The HIV-1 gp120/CXCR4 interaction promotes CCR7-dependent CD4 T cell trafficking into lymph nodes2012

    • Author(s)
      Hayasaka H, Yoshimura H, Kobayashi D, Nakayama EE, Shioda T, Bai Z, Miyasaka M
    • Organizer
      Keystone Symposia
    • Place of Presentation
      (Poster発表)
    • Related Report
      2013 Final Research Report
  • [Presentation] 白血球、癌細胞の生体内動態調節とケモカイン協働作用2011

    • Author(s)
      早坂 晴子
    • Organizer
      新学術領域研究「過渡的複合体」公開シンポジウム
    • Place of Presentation
      東京大学薬学部講堂
    • Year and Date
      2011-07-21
    • Related Report
      2013 Final Research Report
  • [Presentation] 白血球、癌細胞の生体内動態調節とケモカイン共働作用2011

    • Author(s)
      早坂晴子
    • Organizer
      新学術領域研究「過渡的複合体」公開シンポジウム
    • Place of Presentation
      東京大学薬学部講堂(招待講演)
    • Year and Date
      2011-07-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] The effect of HIV-1 gp 120 on CCR7 ligand-induced human CD4 T cell trafficking2010

    • Author(s)
      Hayasaka H
    • Organizer
      第14回国際免疫学会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2010-08-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] ケモカインレセプターの準安定状態と細胞動態2010

    • Author(s)
      早坂 晴子、吉村 洋美、白 忠彬、宮坂 昌之
    • Organizer
      第10回日本蛋白質科学会年会 企画ワークショップ
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2010-06-16
    • Related Report
      2013 Final Research Report
  • [Presentation] The effects of HIV-1 gp120 on CCR7 ligand-induced human CD4 T cell trafficking2010

    • Author(s)
      Hayasaka H, Yoshimura H, Nakayama EE, Shioda T, Bai Z, Miyasaka M
    • Organizer
      第14回 国際免疫学会
    • Place of Presentation
      (口頭発表)
    • Related Report
      2013 Final Research Report
  • [Presentation] Searching for genes that control HEV endothelial cell differentiation2009

    • Author(s)
      早坂晴子
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-12-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] HIV-1外被糖蛋白分子gp120によるCCR7リガンド誘導性ヒトCD4 T細胞ケモタキシスの促進作用2009

    • Author(s)
      早坂晴子
    • Organizer
      日本免疫学会
    • Place of Presentation
      グランキューブ大阪(大阪府)
    • Year and Date
      2009-12-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] 乳癌細胞におけるCXCL12とCCR7リガンド協働作用の解析2009

    • Author(s)
      早坂晴子
    • Organizer
      がん転移学会
    • Place of Presentation
      旭川グランドホテル(北海道)
    • Year and Date
      2009-07-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] ケモカイン受容体多量体形成による細胞動態の調節

    • Author(s)
      早坂 晴子
    • Organizer
      日本生物物理学会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] CXCR4 ligands promote CCR7-dependent CD4 T cell migration- possible involvement of CCR7 oligomerization

    • Author(s)
      早坂 晴子、小林 大地、宮坂 昌之
    • Organizer
      日本免疫学会
    • Place of Presentation
      千葉
    • Related Report
      2013 Annual Research Report
  • [Book] 癌研究と分子標的治療2011

    • Author(s)
      早坂晴子(共著)
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report

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Published: 2009-03-31   Modified: 2018-03-28  

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