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Analysis of signal transduction of Polycythemia vera-associated JAK2 V617F mutant

Research Project

Project/Area Number 21790090
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

TAGO Megumi  Keio University, 薬学部, 講師 (30445192)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
KeywordsJAK2 / V617F点変異 / 真性赤血球増加症 / STAT5 / Akt / Aurora kinase A / V617F変異体 / 抗アポトーシス作用 / 腫瘍形成 / シグナル伝達 / エリスロポエチン
Research Abstract

The constitutively activated mutation of tyrosine kinase JAK2 (V617F) is found in the majority of the patients with polycythemia vera. We found that JAK2 mutant induces transformation through aberrant activation of STAT5. Interestingly, it was found that the expression of Aurora kinase A and activation of Akt were significantly induced by JAK2 mutant. We showed that Aurora kinase A was critical for JAK2 mutant-induced resistance to cisplatin-induced DNA damage. Furthermore, we clarified that Akt activation induced the downregulation of anti-apoptotic proteins, leading to anti-apoptotic activity.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (50 results)

All 2011 2010 2009 Other

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (25 results)

  • [Journal Article] Aurora kinase A critically contributes to the resistance to anti-cancer drug cisplatin in JAK2 V617F mutant-induced transformed cells.2011

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

      FEBS Lett. (in press)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Akt activation through the phosphorylation of erythropoietin receptor at tyrosine 479 is required for myeloproliferative disorder-associated JAK2 V617F mutant-induced cellular transformation.2011

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

      Cell Signal. 23(5)

      Pages: 849-856

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] JAK2 is an important signal transducer in IL-33-induced NF-κB activation.2011

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

      Cell Signal. 23(2)

      Pages: 363-370

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Akt activation through the phosphorylation of erythropoietin receptor at tyrosine 479 is required for myeloproliferative disorder-associated JAK2V617F mutant-induced cellular transformation.2011

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

      Cell Signal.

      Volume: 23(5) Pages: 849-856

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JAK2 is an important signal transducer in IL-33-induced NF-κB activation.2011

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

      Cell Signal.

      Volume: 23(2) Pages: 363-370

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] KappaB-Ras is a nuclear-cytoplasmic small GTPase that inhibits NF-kappaB activation through the suppression of transcriptional activation of p65/RelA.2010

    • Author(s)
      Tago K, Funakoshi-Tago M, Sakinawa M, Mizuno N, Itoh H.
    • Journal Title

      J Biol Chem. 285(40)

      Pages: 30622-30633

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Licochalcones suppress degranulation by decreasing the intracellular Ca2+ level and tyrosine phosphorylation of ERK in RBL-2H3 cells.2010

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

      Int Immunopharmacol. 10(7)

      Pages: 769-776

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The fixed structure of Licochalcone A by alpha, beta-unsaturated ketone is necessary for anti-inflammatory activity through the inhibition of NF-kappaB activation.2010

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

      Int Immunopharmacol. 10(5)

      Pages: 562-571

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Proteolipid protein 2 is associated with melanoma metastasis.2010

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

      Oncol Rep. 23(2)

      Pages: 371-376

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] KappaB-Ras is a nuclear-cytoplasmic small GTPase that inhibits NF-kappaB activation through the suppression of transcriptional activation of p65/RelA.2010

    • Author(s)
      Tago K, Funakoshi-Tago M, Sakinawa M, Mizuno N, Itoh H.
    • Journal Title

      J Biol Chem.

      Volume: 285(40) Pages: 30622-30633

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Licochalcones suppress degranulation by decreasing the intracellular Ca2+ level and tyrosine phosphorylation of ERK in RBL-2H3 cells.2010

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

      Int Immunopharmacol.

      Volume: 10(7) Pages: 769-776

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The fixed structure of Licochalcone A by alpha, beta-unsaturated ketone is necessary for anti-inflammatory activity through the inhibition of NF-kappaB activation.2010

    • 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

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteolipid protein 2 is associated with melanoma metastasis.2010

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

      Oncol Rep.

      Volume: 23(2) Pages: 371-376

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] STAT5 activation is critical for the transformation mediated by myeloproliferative disorder-associated JAK2 V617F mutant.2010

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

      J Biol Chem.

      Volume: 285(8) Pages: 5296-5307

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The fixed structure of Licochalcone A by alpha, beta-unsaturated ketone is necessary for anti-inflammatory activity through the inhibition of NF-kappaB activation.2010

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

      Int Immunopharmacol.(掲載決定)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [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. 285(8)

      Pages: 5296-5307

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pyrrolidinium-type fullerene derivative-induced apoptosis by the generation of reactive oxygen species in HL-60 cells.2009

    • Author(s)
      Nishizawa C, Hashimoto N, Yokoo S, Funakoshi-Tago M, Kasahara T, Takahashi K, Nakamura S, Mashino T.
    • Journal Title

      Free Radic Res. 43(12)

      Pages: 1240-1247

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Licochalcone A potently inhibits tumor necrosis factor alpha-induced nuclear factor-kappaB activation through the direct inhibition of IkappaB kinase complex actuvation.2009

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

      Mol Pharmacol. 76(4)

      Pages: 745-753

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nudemice.2009

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

      Int Immunopharmacol. 9(7-8)

      Pages: 870-877

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit phosphorylation of NF-kappaB p65 in LPS signaling pathway.2009

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

      Int Immunopharmacol. 9(4)

      Pages: 499-507

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The acute lymphoblastic leukemia-associated JAK2 L611S mutant inducestumorigenesis in nude mice.2009

    • 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. 284(19)

      Pages: 12680-90

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Licochalcone A significantly suppresses LPS signaling pathway through the inhibition of NF-kappaB p65 phosphorylation at serine 276.2009

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

      Cell Signal. 21(5)

      Pages: 778-85

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dermatophagoides farinae extract induces severe atopic dermatitis in NC/Nga mice, which is effectively suppressed by the administration of tacrolimus ointment.2009

    • Author(s)
      Oshio T, Sasaki Y, Funakoshi-Tago M, Aizu-Yokota E, Sonoda Y, Matsuoka H, Kasahara T.
    • Journal Title

      Int Immunopharmacol. 9(4)

      Pages: 403-11

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TRAF6 negatively regulates TNFalpha-induced NF-kappaB activation.2009

    • Author(s)
      Funakoshi-Tago M, Kamada N, Shimizu T, Hashiguchi Y, Tago K, Sonoda Y, Kasahara T.
    • Journal Title

      Cytokine. 45(2)

      Pages: 72-9

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] STAT5 activation is critical for the transformation mediated by myeloproliferative disorder-associated JAK2 V617F mutant.

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

      J Biol Chem. 285(8)

      Pages: 5296-5307

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] JAK2変異体(V617F)によるアポトーシス耐性ならびに腫瘍形成能の解析2010

    • Author(s)
      上四元純、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第33回日本分子生物学会年会第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] JAK2変異体(V617F)のシグナル伝達経路に及ぼすSOCS3の役割の解析2010

    • Author(s)
      鶴谷理奈、森脇拓郎、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第33回日本分子生物学会年会第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-11
    • Related Report
      2010 Annual Research Report
  • [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33回日本分子生物学会年会/第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] JAK2変異体(V617F)がc-Mycの恒常的な発現を誘導する2010

    • Author(s)
      鷲見和也、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第33回日本分子生物学会年会/第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Final Research Report
  • [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33回日本分子生物学会年会/第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] JAK2変異体による細胞生存に及ぼすSerine protease inhibitor(Serpin)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33回日本分子生物学会年会/第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] JAK2変異体(V617F)によるアポトーシス耐性ならびに腫瘍形成能の解析2010

    • Author(s)
      上四元純、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第33回日本分子生物学会年会/第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] JAK2変異体(V617F)のシグナル伝達経路に及ぼすSOCS3の役割の解析2010

    • Author(s)
      鶴谷理奈、森脇拓郎、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第33回日本分子生物学会年会/第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Final Research Report
  • [Presentation] JAK2変異体(V617F)がc-Mycの恒常的な発現を誘導する2010

    • Author(s)
      鷲見和也、多胡めぐみ、園田よし子、笠原忠
    • Organizer
      第33回日本分子生物学会年会第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [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33回日本分子生物学会年会第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] JAK2変異体による細胞生存に及ぼすSerine protease inhibitor (Serpin)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33回日本分子生物学会年会第83回日本生化学大会 合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [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33回日本分子生物学会年会第83回日本生化学大会 合同大会
    • Place of Presentation
      東京
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] JAK2変異体のシグナル伝達解析による真性赤血球増加症発症機構の解明2010

    • Author(s)
      多胡めぐみ
    • Organizer
      第54回薬学会関東支部会
    • Place of Presentation
      東京
    • Year and Date
      2010-10-02
    • Related Report
      2010 Final Research Report
  • [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
      2010-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] JAK2変異体(V617F)によるがん化シグナルにおけるPimの役割2010

    • Author(s)
      田中和之、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
      2010-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] JAK2変異体のシグナル伝達解析による真性赤血球増加症発症機構の解明2010

    • Author(s)
      多胡めぐみ
    • Organizer
      第54回 薬学会関東支部会
    • Place of Presentation
      東京
    • Year and Date
      2010-10-02
    • Related Report
      2010 Annual Research Report
  • [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
      2010-10-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] JAK2変異体(V617F)によるがん化シグナルにおけるPimの役割2010

    • Author(s)
      田中和之、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
      2010-10-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] TNFαシグナル伝達に及ぼすFlavonoid化合物の影響The effect of flavonoids on TNFα-induced signaling pathway2010

    • Author(s)
      中村慶, 多胡めぐみ, 園田よし子, 笠原忠
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-30
    • Related Report
      2009 Annual Research Report
  • [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Targetting of FAK and PLP2 by artificial miRNA reduces growth and metastasis of mouse melanoma cells2010

    • 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
    • Year and Date
      2010-03-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 甘草由来Licochalcone AのTNFα誘導性NF-κBの活性化に及ぼす影響The effect of Licochalcone A on TNF α-induced NF-κB activation2010

    • Author(s)
      鶴谷理奈, 中村慶, 多胡めぐみ, 畑中雅史, 増野匡彦, 園田よし子, 笠原忠
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-28
    • Related Report
      2009 Annual Research Report
  • [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The role of Stat5 in signaling pathway induced by polycythemia vera-associated JAK2 V617F mutant2010

    • 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
    • Year and Date
      2010-03-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 4P-219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
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 4P-220真性赤血球増加症患者由来JAK2変異体(V617F)のシグナル伝達経路に及ぼすStat5の役割2009

    • Author(s)
      長田達明, 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
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] 4P-221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
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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