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

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



49 被引用数 (Scopus)


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.

ジャーナルMolecular and Cellular Proteomics
出版ステータスPublished - 2009 2

ASJC Scopus subject areas

  • 分析化学
  • 生化学
  • 分子生物学


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