Hernandez Marylens, Lachmann Alexander, Zhao Shan, Xiao Kunhong, Ma'ayan Avi
Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Proc IEEE Int Symp Bioinformatics Bioeng. 2010;2010:180-184. doi: 10.1109/BIBE.2010.75.
Protein phosphorylation is a reversible post-translational modification commonly used by cell signaling networks to transmit information about the extracellular environment into intracellular organelles for the regulation of the activity and sorting of proteins within the cell. For this study we reconstructed a literature-based mammalian kinase-substrate network from several online resources. The interactions within this directed graph network connect kinases to their substrates, through specific phosphosites including kinasekinase regulatory interactions. However, the "signs" of links, activation or inhibition of the substrate upon phosphorylation, within this network are mostly unknown. Here we show how we can infer the "signs" indirectly using data from quantitative phosphoproteomics experiments applied to mammalian cells combined with the literature-based kinase-substrate network. Our inference method was able to predict the sign for 321 links and 153 phosphosites on 120 kinases, resulting in signed and directed subnetwork of mammalian kinase-kinase interactions. Such an approach can rapidly advance the reconstruction of cell signaling pathways and networks regulating mammalian cells.
蛋白质磷酸化是一种可逆的翻译后修饰，细胞信号网络通常利用它将细胞外环境的信息传递到细胞内细胞器，以调节细胞内蛋白质的活性和分选。在本研究中，我们从多个在线资源重建了一个基于文献的哺乳动物激酶-底物网络。这个有向图网络中的相互作用通过特定的磷酸化位点（包括激酶-激酶调节相互作用）将激酶与其底物连接起来。然而，该网络中连接的“符号”，即磷酸化后底物的激活或抑制，大多是未知的。在这里，我们展示了如何结合应用于哺乳动物细胞的定量磷酸蛋白质组学实验数据和基于文献的激酶-底物网络来间接推断“符号”。我们的推断方法能够预测120种激酶上321个连接和153个磷酸化位点的符号，从而形成哺乳动物激酶-激酶相互作用的有符号和有向子网。这种方法可以迅速推进调节哺乳动物细胞的细胞信号通路和网络的重建。
