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The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src

Research Project

Project/Area Number 20790253
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionOsaka University

Principal Investigator

ONEYAMA Chitose  Osaka University, 微生物病研究所, 助教 (90373208)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsSrc / Csk / Cbp / トランスフォーメーション
Research Abstract

The tyrosine kinase c-Src is upregulated in various human cancers irrespective of its negative regulator Csk, but the regulatory mechanisms remain unclear. In this study, we show that a lipid raft-anchored Csk adaptor, Cbp/PAG, is directly involved in controlling the oncogenicity of c-Src. Using Csk-deficient cells that can be transformed by c-Src overexpression, we found that Cbp expression is markedly downregulated by c-Src activation and re-expression of Cbp efficiently suppresses c-Src transformation as well as tumorigenesis. Cbp-deficient cells are more susceptible to v-Src transformation than their parental cells. Upon phosphorylation, Cbp specifically binds to activated c-Src and sequesters it in lipid rafts, resulting in an efficient suppression of c-Src function independent of Csk. In some human cancer cells and tumors, Cbp is downregulated and the introduction of Cbp significantly suppresses tumorigenesis. These findings indicate a potential role for Cbp as a suppressor of c-Src-mediated tumor progression.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (15 results)

All 2009 2008 Other

All Journal Article (12 results) (of which Peer Reviewed: 10 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Transforming potential of Src family kinases is limited by the cholesterol-enriched membrane microdomain2009

    • Author(s)
      Oneyama C, Iino T, Saito K, Suzuki K, Ogawa A, Okada M.
    • Journal Title

      Mol Cell Biol 29

      Pages: 6262-6272

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A versatile non-viral vector system for tetracycline-dependent one-step conditional induction of transgene expression2009

    • Author(s)
      Inoue K, Sone T, Oneyama C, Nishiumi F, Kishine H, Sasaki Y, Andoh T, Okada M, Chesnut JD, Imamoto F.
    • Journal Title

      Gene Therapy 16(12)

      Pages: 1383-1394

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling2009

    • Author(s)
      Enomoto M, Hayakawa S, Itsukushima S, Ren DY, Matsuo M, Tamada K, Oneyama C, Okada M, Takumi T, Nishita M, Minami Y
    • Journal Title

      Oncogene 28(36)

      Pages: 3197-3208

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] 細胞膜ミクロドメイン「ラフト」を介するSrcがん化シグナル制御機構2009

    • Author(s)
      小根山千歳、岡田雅人
    • Journal Title

      蛋白質核酸酵素 54(3)

      Pages: 201-211

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transforming potential of Src family kinases is limited by the cholesterol-enriched membrane microdomain.2009

    • Author(s)
      Oneyama Chitose
    • Journal Title

      Mol Cell Biol 29

      Pages: 6462-72

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A versatile nonviral vector system for tetracycline-dependent one-step conditional induction of transgene expression.2009

    • Author(s)
      Inoue Ken
    • Journal Title

      Gene Therapy 16

      Pages: 1383-1394

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autonomous regulation of osteosarcoma cell invasiveness by Wnt5a/Ror2 signaling.2009

    • Author(s)
      Enomoto Masahiro
    • Journal Title

      Oncogene 28

      Pages: 3197-3208

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞膜ミクロドメイン「ラフト」を介するSrcがん化シグナル制御機構2009

    • Author(s)
      小根山千歳, ら
    • Journal Title

      蛋白質核酸酵素 54

      Pages: 201-211

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src2008

    • Author(s)
      Oneyama C, Hikita T, Enya K, Dobenecker MW, Saito K, Nada S, Tarakhovsky A, Okada M.
    • Journal Title

      Mol Cell 30(4)

      Pages: 426-36

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] チロシンキナーゼシグナルとがん形質発現2008

    • Author(s)
      小根山千歳、岡田雅人
    • Journal Title

      実験医学増刊号「シグナル伝達2008-2009」 26(15)

      Pages: 41-48

    • Related Report
      2009 Final Research Report
  • [Journal Article] The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src2008

    • Author(s)
      Oneyama C, et.al.
    • Journal Title

      Mol Cell 30

      Pages: 426-436

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] チロシンキナーゼシグナルとがん形質発現2008

    • Author(s)
      小根山千歳, ら
    • Journal Title

      実験医学 26

      Pages: 41-48

    • Related Report
      2008 Annual Research Report
  • [Presentation] 細胞膜ミクロドメイン"ラフト"におけるSrcファミリーの制御とがん形質発現2009

    • Author(s)
      小根山千歳、飯野琢也、斎藤一伸、鈴木慶、岡田雅人
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-10
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] ラフトにおけるSrcファミリーの制御とがん形質発現2008

    • Author(s)
      小根山千歳、疋田智也、塩谷健悟、岡田雅人
    • Organizer
      BMB2008
    • Place of Presentation
      神戸
    • Year and Date
      2008-12-11
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.biken.osaka-u.ac.jp/biken/oncogene/Top.html

    • Related Report
      2009 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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