Temporal Perturbation of Tyrosine Phosphoproteome Dynamics Reveals the System-wide Regulatory Networks
Temporal Perturbation of Tyrosine Phosphoproteome Dynamics Reveals the System-wide Regulatory Networks
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DOI：
10.1074/mcp.m800186-mcp200
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发表时间：
2009-02-01
影响因子：
7
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
--
作者：
Oyama, Masaaki;Kozuka-Hata, Hiroko;Yamamoto, Tadashi
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. Molecular & Cellular Proteomics 8:226-231, 2009.
