Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data
Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data
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DOI：
10.1111/gtc.12655
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发表时间：
2019-01-01
期刊：
影响因子：
2.1
通讯作者：
Kuroda, Shinya
中科院分区：
文献类型：
--
作者：
Kawata, Kentaro;Yugi, Katsuyuki;Kuroda, Shinya
细胞信号通过蛋白质磷酸化调节各种细胞功能。磷酸化蛋白质组学数据可能包括从信号传导到细胞功能的全球调节网络的信息，但是使用这些数据重建该网络的程序尚未建立。在本文中，我们提供了一个程序来重建一个全球性的调控网络，从信号到细胞功能的磷酸化蛋白质组学数据整合先验知识的细胞功能和推理的激酶底物关系（KSRs）。我们使用来自胰岛素刺激的Fao肝癌细胞的磷酸化蛋白质组学数据，并在KEGG数据库中确定了由胰岛素特异性过度表达的细胞功能调节的蛋白质磷酸化。我们推断KSR的蛋白磷酸化激酶，并将胰岛素信号层中的激酶与细胞功能中的磷酸化蛋白联系起来，揭示胰岛素信号分别通过Pi 3 k-Akt和Erk信号通路选择性地传递到细胞粘附和RNA成熟。因此，我们提供了一种基于磷酸化蛋白质组学数据重建从信号传导到细胞功能的全局调控网络的方法。
Cellular signaling regulates various cellular functions via protein phosphorylation. Phosphoproteomic data potentially include information for a global regulatory network from signaling to cellular functions, but a procedure to reconstruct this network using such data has yet to be established. In this paper, we provide a procedure to reconstruct a global regulatory network from signaling to cellular functions from phosphoproteomic data by integrating prior knowledge of cellular functions and inference of the kinase-substrate relationships (KSRs). We used phosphoproteomic data from insulin-stimulated Fao hepatoma cells and identified protein phosphorylation regulated by insulin specifically over-represented in cellular functions in the KEGG database. We inferred kinases for protein phosphorylation by KSRs, and connected the kinases in the insulin signaling layer to the phosphorylated proteins in the cellular functions, revealing that the insulin signal is selectively transmitted via the Pi3k-Akt and Erk signaling pathways to cellular adhesions and RNA maturation, respectively. Thus, we provide a method to reconstruct global regulatory network from signaling to cellular functions based on phosphoproteomic data.