Reconstruction of insulin signal flow from phosphoproteome and metabolome data
Reconstruction of insulin signal flow from phosphoproteome and metabolome data
复制标题
从磷酸化蛋白质组和代谢组数据重建胰岛素信号流
DOI：
10.1016/j.celrep.2014.07.021
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
S.
中科院分区：
文献类型：
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作者：
Yugi;K.;Kubota;H.;Toyoshima;Y.;Noguchi;R.;Kawata;K.;Komori;Y.;Uda;S.; Kunida;K.;Tomizawa;Y.;Funato;Y.;Miki;H.;Matsumoto;M.;Nakayama;K.I.;Kashikura;K.;Endo;K.;Ikeda;K.;Soga;T.;Kuroda;S.
细胞内稳态是由信号通过多个分子网络，包括蛋白质磷酸化和代谢产物的调节。然而，信号在何处以及何时流经网络并调节稳态尚未被探索。我们已经开发了一种重建方法的信号流的基础上的时间过程磷酸化蛋白质组和代谢组数据，使用多个数据库，并已将其应用到胰岛素，代谢稳态的重要激素的急性作用。胰岛素信号流经一个网络，通过涉及13种蛋白激酶、26种磷酸化代谢酶和35种变构效应物的信号通路，导致44种代谢物的定量变化。对网络的分析表明，胰岛素诱导磷酸化和激活肝型磷酸果糖激酶1，从而控制糖酵解中的关键反应。因此，我们提供了一个通用的方法，通过网络使用磷酸化蛋白质组和代谢组数据的信号流重建。
Cellular homeostasis is regulated by signals through multiple molecular networks that include protein phosphorylation and metabolites. However, where and when the signal flows through a network and regulates homeostasis has not been explored. We have developed a reconstruction method for the signal flow based on time-course phosphoproteome and metabolome data, using multiple databases, and have applied it to acute action of insulin, an important hormone for metabolic homeostasis. An insulin signal flows through a network, through signaling pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes, and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites. Analysis of the network reveals that insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, thereby controlling a key reaction in glycolysis. We thus provide a versatile method of reconstruction of signal flow through the network using phosphoproteome and metabolome data.