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2011 Fiscal Year Final Research Report

Investigation of abnormal cytokine signaling and the development of the drugs modulating these signaling

Research Project

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Project/Area Number 21590072
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKeio University

Principal Investigator

KASAHARA Tadashi  慶應義塾大学, 薬学部, 教授 (60049096)

Co-Investigator(Kenkyū-buntansha) TAGO Megumi  慶應義塾大学, 薬学部, 講師 (30445192)
Project Period (FY) 2009 – 2011
Keywords接着班キナーゼFAK / JAKキナーゼ / JAK2 V617F変異体 / Epoシグナル / STAT5の恒常的な活性化 / 腫瘍形成能 / リコカルコンA
Research Abstract

(1) We previously reported that a FAKY929F mutant in the B16F10 melanoma cell line gave poor metastasis. Here, we identified that the phospholipid protein(PLP) 2 was downregulated in this cell line, acting as an effector molecule downstream of FAK. Why PLP2 induces the metastatic activity was investigated in vitro and in vivo.(2) A JAK2 mutant, JAK2V617F was constitutively active and induced abnormal proliferation, tumorigenesis in nude mice, as well as exhibited resistance to antitumor drugs including cisplatin. The reason why JAK2V617F has such potent activities was studied. We presented a notion that JAK2 mutation constitutively activated STAT5, which enhanced various transcription factors and kinases including c-Myc, Aurora kinaseA or Pim-1/2, thus inducing transformation in vitro and in vivo.

  • Research Products

    (33 results)

All 2012 2011 2010 2009 Other

All Journal Article (14 results) Presentation (12 results) Book (6 results) Remarks (1 results)

  • [Journal Article] Pyrvinium pamoate inhibits proliferation of myeloma/erythroleukemia cells by suppressing mitochondrial respiratory complex I and STAT32012

    • Author(s)
      Harada Y, Ishii I, Hatake K, Kasahara T.
    • Journal Title

      Cancer Lett

      Volume: 319(1) Pages: 83-88

  • [Journal Article] Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells2011

    • Author(s)
      Sumi K, Tago K, Kasahara T, Funakoshi-Tago M.
    • Journal Title

      FEBS Lett

      Volume: 585(12) Pages: 1884-1890

  • [Journal Article] Anti-inflammatory ac tivity of structurally related flavonoids, Apige nin, Luteolin and Fisetin2011

    • Author(s)
      Funakoshi-Tago M, Nakamura K, Tago K, MashinoT, Kasahara T.
    • Journal Title

      Int Immunopharmacol

      Volume: 11(9) Pages: 1150-1159

  • [Journal Article] Akt activation through the ph osphorylation of erythropoietin receptor at tyr osine 479 is required for myeloproliferative d isorder-associated JAK2 V617F mutant-induce d cellular transformation2011

    • Author(s)
      Kamishimoto J, Tago K, Kasahara T, Fun akoshi-Tago M.
    • Journal Title

      Cell Signal

      Volume: 23(5) Pages: 849-856

  • [Journal Article] JAK2 is an important signal transducer in IL-33-induced NF-κB activation2011

    • Author(s)
      Funakoshi-Tago M, Tago K, Sato Y, Tominaga S, Kasahara T.
    • Journal Title

      Cell Signal

      Volume: 23(2) Pages: 263-270

  • [Journal Article] The fixed structure of Licochalcone A by alpha, beta-unsaturated ketone is necessary for anti-inflammatory activity through the inhibition of NF-kB activation2010

    • Author(s)
      Funakoshi-Tago M, Nakamura K, Tsuruya R, Hatanaka M, Mashino T, Sonoda Y, Kasahara T.
    • Journal Title

      Int Immunopharmacol

      Volume: 10(5) Pages: 562-571

  • [Journal Article] STAT5 activation is critical for the transformation mediated by myeloproliferative disorder-associated JAK2 V617F Mutant2010

    • Author(s)
      Funakoshi-Tago M, Tago K, Abe M, Sonoda Y, Kasahara T.
    • Journal Title

      J Biol Chem.

      Volume: 258(8) Pages: 5296-5307

  • [Journal Article] Proteolipid protein 2 is associated with melanoma metastasis2010

    • Author(s)
      Sonoda Y, Warita M, Suzuki T, Ozawa H, Fukuda Y, Funakoshi-Tago M, Kasahara T.
    • Journal Title

      Oncol Report

      Volume: 23(2) Pages: 371-376

  • [Journal Article] Licochalcones suppress degranulation by decreasing the intracellular Ca^<2+> level and tyrosine phosphorylation of ERK in RBL-2H3 cells2010

    • Author(s)
      Tanifuji S, Aizu-Yokota E, Funakoshi-Tago M, Sonoda Y, Inoue H, Kasahara T.
    • Journal Title

      Int Immunopharmacol

      Volume: 10(7) Pages: 769-770

  • [Journal Article] A potently inhibits TNFa-induced NF-kB activation through the direct inhibition of IkB kinase complex activation2009

    • Author(s)
      Funakoshi-Tago M, Tanabe S, Tago K, Itoh H, Mashino T, Sonoda Y, Kasahara T
    • Journal Title

      Mol Pharmacol

      Volume: 76(4) Pages: 745-753

  • [Journal Article] The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nude mice2009

    • Author(s)
      Abe M, Funakoshi-Tago M, Tago K, Kamishimoto J, Aizu-Yokota E, Sonoda Y, Kasahara T
    • Journal Title

      Int Immunopharmacol

      Volume: 9(7-8) Pages: 870-877

  • [Journal Article] The acute lymphoblastic leukemia-associated JAK2 L611S mutant induces tumorigenesis in nude mice2009

    • Author(s)
      Funakoshi-Tago M, Tago K, Sumi K, Abe M, Aizu-Yokota E, Oshio T, Sonoda Y, Kasahara T.
    • Journal Title

      J Biol Chem

      Volume: 284(19) Pages: 12680-12690

  • [Journal Article] Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit phosphorylation of NF-kB p65 in LPS signaling pathway2009

    • Author(s)
      Furusawa J, Funakoshi-Tago M, Mashino T, Tago K, Sonoda Y, Kasahara T.
    • Journal Title

      Int Immunopharmacol

      Volume: 9(4) Pages: 499-507

  • [Journal Article] Licochalcone A significantly suppresses LPS signaling pathway through the inhibition of NF-kappaB p65 phosphorylation at serine 2762009

    • Author(s)
      Furusawa J, Funakoshi-Tago M, Tago K, Mashino T, Inoue H, Sonoda Y, Kasahara T.
    • Journal Title

      Cell Signal

      Volume: 21(5) Pages: 778-785

  • [Presentation] 慢性骨髄増殖性腫瘍由来JAK2変異体のシグナル伝達におけるCISの機能解析2011

    • Author(s)
      森脇拓郎、岡本一飛、多胡めぐみ、笠原忠
    • Organizer
      第10回次世代を担う若手ファーマ・バイオフォーラム2011
    • Place of Presentation
      仙台市
    • Year and Date
      2011-10-09
  • [Presentation] JAK2新規リン酸化部位Y423の同定および機能解析2011

    • Author(s)
      村上はるか、上四元純、多胡めぐみ、笠原忠
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都市
    • Year and Date
      2011-09-23
  • [Presentation] 慢性骨髄増殖性腫瘍由来JAK2変異体のシグナル伝達経路におけるc-Mycの役割2011

    • Author(s)
      庄司貴一、鷲見和也、多胡めぐみ、笠原忠
    • Organizer
      第12回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      富山市
    • Year and Date
      2011-06-17
  • [Presentation] フラーレン誘導体を用いた慢性骨髄増殖性腫瘍の治療法の開発2011

    • Author(s)
      田中和之、長田達明、多胡めぐみ、中村成夫、増野匡彦、笠原忠
    • Organizer
      第12回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      富山市
    • Year and Date
      2011-06-17
  • [Presentation] FAK及びPLP2ノックダウンによるメラノーマ増殖抑制について2010

    • Author(s)
      小澤広規、保科直美、多胡めぐみ、園田よし子, 笠原忠
    • Organizer
      第83回日本生化学大会
    • Place of Presentation
      神戸市
    • Year and Date
      2010-12-04
  • [Presentation] JAK2変異体のシグナル伝達におけるPimの役割の解析2010

    • Author(s)
      田中和之、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第83回日本生化学大会
    • Place of Presentation
      神戸市
    • Year and Date
      2010-12-04
  • [Presentation] 真性赤血球増加症由来JAK2変異体のシグナル伝達におけるc-Mycの役割2010

    • Author(s)
      鷲見和也、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第54回薬学会関東支部会
    • Place of Presentation
      東京
    • Year and Date
      2010-10-15
  • [Presentation] 真性赤血球増加症におけるセリン・プロテアーゼインヒビター群の役割2010

    • Author(s)
      長田達明、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第11回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2010-06-17
  • [Presentation] FAK及びPLP2ノックダウンによるメラノーマ転移抑制について2010

    • Author(s)
      小澤広規、園田よし子、多胡めぐみ、笠原忠
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山市
    • Year and Date
      2010-03-28
  • [Presentation] 真性赤血球増加症由来JAK2変異体(V617F)のシグナル伝達経路に及ぼすSTAT5の役割2010

    • Author(s)
      多胡めぐみ、阿部美雪、園田よし子、笠原忠
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山市
    • Year and Date
      2010-03-28
  • [Presentation] 真性赤血球増加症由来JAK2変異体(V617F)によるファンコニ貧血原因遺伝子群の発現誘導2009

    • Author(s)
      鷲見和也、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第82回日本生化学大会
    • Place of Presentation
      神戸市
    • Year and Date
      2009-10-24
  • [Presentation] 真性赤血球増加症由来JAK2点変異(V617F)によるアポトーシス耐性機構の解析2009

    • Author(s)
      上四元純、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第82回日本生化学大会
    • Place of Presentation
      神戸市
    • Year and Date
      2009-10-24
  • [Book] 臨床免疫・アレルギー科(総説、ケモカイン:エオタキシン-1/CCL11)2012

    • Author(s)
      笠原忠
    • Publisher
      科学評論社
  • [Book] 「疾病と病態」改訂第3版2012

    • Author(s)
      笠原忠
    • Total Pages
      305-326
    • Publisher
      南江堂
  • [Book] ヒューマニズム薬学入門2012

    • Author(s)
      笠原忠
    • Total Pages
      33-42, 71-79
    • Publisher
      培風館
  • [Book] L-33レセプターのシグナル伝達、臨床免疫・アレルギー科2011

    • Author(s)
      笠原忠、多胡めぐみ
    • Total Pages
      359-364
    • Publisher
      科学評論社
  • [Book] からだの科学2009

    • Author(s)
      笠原忠
    • Total Pages
      148-151
    • Publisher
      日本評論社
  • [Book] 炎症・再生医学事典2009

    • Author(s)
      笠原忠、多胡めぐみ
    • Total Pages
      52-54
    • Publisher
      朝倉書店
  • [Remarks]

    • URL

      http://www.pha.keio.ac.jp/laboratory/laboratory14.html

URL: 

Published: 2013-07-31  

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