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Analysis of signal transduction in glycolipid microdomains

Research Project

Project/Area Number 26440071
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional biochemistry
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KASAHARA Kohji  公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副室長 (60250213)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords脂質ラフト / 糖脂質ミクロドメイン / シグナル伝達 / ラフト / 血小板
Outline of Final Research Achievements

SDF-1α-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and PI3K. Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α-induced platelet aggregation is inhibited by pretreatment with the Akt inhibitor MK-2206 in a dose-dependent manner. Furthermore,SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the raft-disrupting agent methyl-β-cyclodextrin. Sucrose density gradient analysis shows that 35% of CXCR4, 93% of the heterotrimeric G proteins Gαi-1, 91% of Gαi-2, 50% of Gβ and 4.0% of PI3Kβ, and 4.5% of Akt2 are localized in the detergent-resistant membrane raft fraction. These findings suggest that SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3K-dependent Akt phosphorylation.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (18 results)

All 2017 2016 2015 2014 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Book (3 results) Remarks (2 results)

  • [Journal Article] SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3 kinase-dependent Akt phosphorylation.2017

    • Author(s)
      Ohtsuka H, Iguchi T, Hayashi M, Kaneda M, Iida K, Shimonaka M, Hara T, Arai M, Koike Y, Yamamoto N, Kasahara K.
    • Journal Title

      PLoS One

      Volume: 12 Issue: 1 Pages: e0169609-e0169609

    • DOI

      10.1371/journal.pone.0169609

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] G alpha o2017

    • Author(s)
      Iguchi T, Kasahara K.
    • Journal Title

      Encyclopedia of Signaling Molecules, 2nd Edition Springer Sangdun Choi Eds.

      Volume: 2 Pages: 1891-1899

    • DOI

      10.1007/978-3-319-67199-4_101497

    • ISBN
      9783319671987, 9783319671994
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NMDA型グルタミン酸受容体の生理機能2015

    • Author(s)
      笠原浩二
    • Journal Title

      臨床神経科学

      Volume: 33(1) Pages: 22-24

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transbilayer distribution of lipids at nano scale.2015

    • Author(s)
      Murate M, Abe M, Kasahara K, Iwabuchi K, Umeda M, Kobayashi T
    • Journal Title

      J Cell Sci

      Volume: 128 Pages: 1627-1638

    • DOI

      10.1242/jcs.163105

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Lipid rafts and anti-glycolipid antibodies.2014

    • Author(s)
      Kasahara K
    • Journal Title

      Trend.Glycosci.Glycotech.

      Volume: 26 Pages: 79-87

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] TAG-1リガンド/ホスファカンのコンドロイチン硫酸CSCによる小脳顆粒細胞反発作用2017

    • Author(s)
      小松谷啓介、井口智弘、川島育夫、武田泰生、霜田靖、杉浦信夫、前田信明、笠原浩二
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血餅退縮における硫酸化スフィンゴ糖脂質スルファチドの機能解析2016

    • Author(s)
      井口智弘 、林もゆる、兼田瑞穂、大塚拡子、下仲基之、山本正雅、山下竜幸、本家孝一 、笠原浩二
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 血餅退縮における硫酸化スフィンゴ糖脂質スルファチドの機能2016

    • Author(s)
      林もゆる、兼田瑞穂、大塚拡子、下仲基之、山本正雅、笠原浩二
    • Organizer
      第38回日本血栓止血学会
    • Place of Presentation
      春日野国際フォーラム甍(奈良県奈良市)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 血小板スフィンゴ脂質ドメイン/脂質ラフトを介する血餅退縮メカニズム2016

    • Author(s)
      笠原浩二、本家孝一
    • Organizer
      タイムシグナルと制御シンポジウム
    • Place of Presentation
      筑波大学下田臨海実験センター(静岡県下田市)
    • Year and Date
      2016-06-10
    • Related Report
      2016 Research-status Report
  • [Presentation] Fibrin Clot Retraction is Mediated by Platelet Membrane Rafts2016

    • Author(s)
      Kasahara K.
    • Organizer
      1st Korea-Japan Bioactive Lipid Joint Symposium
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      2016-05-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ケモカインSDF-1αの血小板スルファチドラフトを介するシグナル伝達の可能性2015

    • Author(s)
      大塚拡子、林もゆる、下仲基之、山本正雅、笠原浩二
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2015-07-31
    • Related Report
      2015 Research-status Report
  • [Presentation] ケモカインSDF-1αの血小板脂質ラフトを介するシグナル伝達2015

    • Author(s)
      大塚拡子、兼田瑞穂、下仲基之、山本正雅、笠原浩二
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府市総合市民会館(山梨県甲府市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 細胞膜の内外層および膜面における脂質分子種の非対称分布の解析2014

    • Author(s)
      村手源英、阿部充宏、笠原浩二、岩渕和久、梅田真郷、小林俊秀
    • Organizer
      電子顕微鏡イメージングの医学・生物
    • Place of Presentation
      生理学研究所(愛知県岡崎市)
    • Year and Date
      2014-11-12
    • Related Report
      2014 Research-status Report
  • [Book] Encyclopedia of Signaling Molecules, 2nd Edition2017

    • Author(s)
      Iguchi T, Kasahara K.
    • Total Pages
      9
    • Publisher
      Springer
    • Related Report
      2016 Research-status Report
  • [Book] Transglutaminases doi:10.1007/978-4-431-55825-5_152015

    • Author(s)
      Hayashi M, Kasahara K
    • Total Pages
      14
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report
  • [Book] Glycoscience: Biology and Medicine2015

    • Author(s)
      Kasahara K
    • Total Pages
      6
    • Publisher
      Springer
    • Related Report
      2014 Research-status Report
  • [Remarks]

    • URL

      http://www.igakuken.or.jp/biomembrane/index.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 細胞膜研究室ホームページ

    • URL

      http://www.igakuken.or.jp/biomembrane/

    • Related Report
      2016 Research-status Report 2015 Research-status Report 2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2023-03-16  

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