Crosstalk between signaling pathways provided by single and multiple protein phosphorylation sites.
Crosstalk between signaling pathways provided by single and multiple protein phosphorylation sites.
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DOI：
10.1016/j.jmb.2014.11.001
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发表时间：
2015-01-30
影响因子：
5.6
通讯作者：
Panchenko, Anna R.
中科院分区：
文献类型：
--
作者：
Nishi, Hafumi;Demir, Emek;Panchenko, Anna R.
细胞命运取决于磷酸化事件提供的信号传导过程的时空分离和整合。在这项研究中，我们确定了信号串扰的关键点，它可以由单个靶蛋白上的离散磷酸化事件触发。我们整合了个人的磷酸化位点的数据，其相应的激酶的证据，磷酸化对靶蛋白活性的功能后果和相应的途径。我们的研究结果表明，有相当一部分的磷酸化位点，可以发挥关键作用的替代或冗余的途径和磷酸化的调节结果之间的串扰可以连接到一种类型的磷酸化残基。这些调节磷酸化位点可以作为信号流中的枢纽，其功能作用与其特定性质直接相关。也就是说，具有相似调节功能的磷酸化位点被相同的激酶磷酸化，并参与相似生化途径的调节。这些位点更可能在序列和空间上聚集，不像在靶蛋白上磷酸化具有拮抗结果的位点。此外，我们发现具有相似功能结果的位点的计算机磷酸化对靶蛋白稳定性具有可比的结果。磷酸化位点在生物串扰中的重要作用从其进化保守性的分析中显而易见。
Cellular fate depends on the spatio-temporal separation and integration of signaling processes which can be provided by phosphorylation events. In this study we identify the crucial points in signaling crosstalk which can be triggered by discrete phosphorylation events on a single target protein. We integrated the data on individual human phosphosites with the evidence on their corresponding kinases, the functional consequences on phosphorylation on activity of the target protein and corresponding pathways. Our results show that there is a substantial fraction of phosphosites that can play critical roles in crosstalk between alternative or redundant pathways and regulatory outcome of phosphorylation can be linked to a type of phosphorylated residue. These regulatory phosphosites can serve as hubs in the signal flow and their functional roles are directly connected to their specific properties. Namely, phosphosites with similar regulatory functions are phosphorylated by the same kinases and participate in regulation of similar biochemical pathways. Such sites are more likely to cluster in sequence and space unlike sites with antagonistic outcomes of their phosphorylation on a target protein. In addition we found that in silico phosphorylation of sites with similar functional consequences have comparable outcomes on a target protein stability. An important role of phosphorylation sites in biological crosstalk is evident from the analysis of their evolutionary conservation.
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影响因子：
3.7
作者：
Nishi H;Shaytan A;Panchenko AR
通讯作者：
Panchenko AR
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
通讯作者：
Tanabe M
影响因子：
5.6
作者：
Guerois, R;Nielsen, JE;Serrano, L
通讯作者：
Serrano, L
影响因子：
14.9
作者：
Hornbeck PV;Kornhauser JM;Tkachev S;Zhang B;Skrzypek E;Murray B;Latham V;Sullivan M
通讯作者：
Sullivan M
影响因子：
64.8
作者：
Jeong, H;Mason, SP;Oltvai, ZN
通讯作者：
Oltvai, ZN