Temporal perturbation of tyrosine phosphoproteome dynamics reveals the system-wide regulatory networks

Masaaki Oyama, Hiroko Kozuka-Hata, Shinya Tasaki, Kentaro Senba, Seisuke Hattori, Sumio Sugano, Jun Ichiro Inoue, Tadashi Yamamoto

    Research output: Contribution to journalArticle

    46 Citations (Scopus)

    Abstract

    Signal transduction systems are known to widely regulate complex biological events such as cell proliferation and differentiation. Because phosphotyrosine-dependent networks play a key role in transmitting signals, a comprehensive and fine description of their dynamic behavior can lead us to systematically analyze the regulatory mechanisms that result in each biological effect. Here we established a mass spectrometry-based framework for analyzing tyrosine phosphoproteome dynamics through temporal network perturbation. A highly time-resolved description of the epidermal growth factor-dependent signaling pathways in human A431 cells revealed a global view of their multiphase network activation, comprising a spike signal transmission within 1 min of ligand stimulation followed by the prolonged activation of multiple Src-related molecules. Temporal perturbation of Src family kinases with the corresponding inhibitor PP2 in the prolonged activation phase led to the down-regulation of the molecules related to cell adhesion and receptor degradation, whereas the canonical cascades as well as the epidermal growth factor receptor relatively maintained their activities. Our methodology provides a system-wide view of the regulatory network clusters involved in signal transduction that is essential to refine the literature-based network structures for a systems biology analysis.

    Original languageEnglish
    Pages (from-to)226-231
    Number of pages6
    JournalMolecular and Cellular Proteomics
    Volume8
    Issue number2
    DOIs
    Publication statusPublished - 2009 Feb

    Fingerprint

    Tyrosine
    Signal transduction
    Chemical activation
    Signal Transduction
    Phosphotyrosine
    Molecules
    Systems Biology
    src-Family Kinases
    Cell adhesion
    Cell proliferation
    Epidermal Growth Factor Receptor
    Epidermal Growth Factor
    Cell Adhesion
    Mass spectrometry
    Cell Differentiation
    Mass Spectrometry
    Down-Regulation
    Cell Proliferation
    Ligands
    Degradation

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Analytical Chemistry

    Cite this

    Temporal perturbation of tyrosine phosphoproteome dynamics reveals the system-wide regulatory networks. / Oyama, Masaaki; Kozuka-Hata, Hiroko; Tasaki, Shinya; Senba, Kentaro; Hattori, Seisuke; Sugano, Sumio; Inoue, Jun Ichiro; Yamamoto, Tadashi.

    In: Molecular and Cellular Proteomics, Vol. 8, No. 2, 02.2009, p. 226-231.

    Research output: Contribution to journalArticle

    Oyama, Masaaki ; Kozuka-Hata, Hiroko ; Tasaki, Shinya ; Senba, Kentaro ; Hattori, Seisuke ; Sugano, Sumio ; Inoue, Jun Ichiro ; Yamamoto, Tadashi. / Temporal perturbation of tyrosine phosphoproteome dynamics reveals the system-wide regulatory networks. In: Molecular and Cellular Proteomics. 2009 ; Vol. 8, No. 2. pp. 226-231.
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