New Functional Proteins Identified by Proteomic Analysis in the Epidermal Growth Factor Receptor-mediated Signaling Pathway and Application for Practical Use

  • TASHIRO Kyoko
    Center for Drug Discovery, Graduated School of Pharmaceutical Sciences, University of Shizuoka
  • KONISHI Hiroaki
    Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima
  • NABESHI Hiromi
    Graduate School of Pharmaceutical Sciences, Osaka University
  • YAMAUCHI Emiko
    Division of Disease Proteomics, Institute for Enzyme Research, the University of Tokushima
  • TANIGUCHI Hisaaki
    Division of Disease Proteomics, Institute for Enzyme Research, the University of Tokushima

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Other Title
  • 上皮細胞成長因子(EGF)受容体下流におけるシグナル伝達分子のプロテオミクス解析により同定した新規タンパク質とそのバイオマーカーへの応用の可能性
  • ジョウヒ サイボウ セイチョウ インシ EGF ジュヨウタイ カリュウ ニ オケル シグナル デンタツ ブンシ ノ プロテオミクス カイセキ ニ ヨリ ドウテイ シタ シンキ タンパクシツ ト ソノ バイオマーカー エ ノ オウヨウ ノ カノウセイ

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Abstract

  To clarify the whole picture of epidermal growth factor (EGF) signaling pathway, we identified proteins from the EGF-stimulated A431 cells by anti-phospho-tyrosine antibody column chromatography. Over 150 proteins were detected including previously unidentified proteins as well as well-studied proteins. Among these proteins, we picked up four proteins that had not been known in EGF signaling pathway and analyzed their functions. We report the functions of these proteins in this article. 1) CFBP interacts with CD2AP family proteins and functions as a key component in downregulation of EGF receptor protein level following EGF stimulation. 2) Ymer is found to be phosphorylated and ubiquitinated upon EGF stimulation, and functions as a regulator for the downregulation and endocytosis of EGF receptor. 3) CLPABP binds to mitochondria-specific phospholipids, cardiolipin, through its PH domain, and its complex includes various proteins related to mRNA metabolism. 4) GAREM is associated with Grb2 and Shp2. Each association affects the ERK activity. Finally, we discuss the possibilities that these proteins can be used as a novel biomarker protein for cancer and other diseases.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 130 (4), 471-477, 2010-04-01

    The Pharmaceutical Society of Japan

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