Building and exploring an integrated human kinase network: global organization and medical entry points.
Building and exploring an integrated human kinase network: global organization and medical entry points.
复制标题
建立和探索一个集成的人类激酶网络：全球组织和医疗入口点。
DOI：
10.1016/j.jprot.2014.03.028
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发表时间：
2014-07-31
影响因子：
3.3
通讯作者：
Superti-Furga G
中科院分区：
文献类型：
--
作者：
Colinge J;César-Razquin A;Huber K;Breitwieser FP;Májek P;Superti-Furga G
生物物质被组织成不同性质的功能网络，其中激酶-底物和蛋白质-蛋白质相互作用发挥着重要作用。大量的公共数据收集使我们能够编制有关人类蛋白激酶的重要相互作用数据集。分析该网络的最有趣的观察结果之一是，激酶功能活性的一致性主要依赖于激酶底物相互作用，而不是依赖于它们周围形成的蛋白质复合物。进一步剖析激酶组（CMGC、酪氨酸激酶等）水平上的两种相互作用，我们发现组内互连性很普遍，我们可以自然地将其与生物网络进化的当前场景联系起来。跟踪发表日期，我们观察到激酶相互作用研究重点与一般激酶研究高度相关。我们发现激酶抑制剂的靶标也存在类似的偏差，具有高冗余性。最后，将激酶抑制剂特异性与位于激酶网络中特定位置的激酶组相交叉，我们为使用这些化合物的未来治疗策略提出了替代选择。尽管蛋白激酶对细胞调节很重要，而且蛋白激酶是现代治疗方法的突出靶标，但整体整合蛋白磷酸化网络的结构和逻辑尚未得到深入研究。为了关注磷酸化网络的调控骨架，我们设想了一个由激酶、其底物和公开的物理蛋白质相互作用组成的网络。对该网络的多个层面的分析允许建立一系列有趣的特性，例如激酶底物相互作用的普遍性，而不是一般的蛋白质-蛋白质相互作用，以建立对激酶活性的整体控制。除非激酶外，控制许多或仅少数其他激酶的激酶在细胞区室中的分布也不同。它们还成为激酶抑制剂的靶标，并取得了显着的成功率。受大量激酶严格调控的非激酶参与特定的生物过程并与其调节因子共享，同时优选位于细胞核中。总的来说，这些观察结果可能为制定药理干预策略提供新的视角。与有关这些酶的一般研究相比，我们从如何生成此类数据的角度补充了对激酶相互作用的研究。即，研究界对基于相互作用的激酶实验和基于非相互作用的激酶实验的关注的时间演变是怎样的。本文是特刊的一部分，题为：纪念维塔利亚诺·帕里尼 (Vitaliano Pallini) 的蛋白质组学 20 年。客座编辑：Luca Bini、Juan J. Calvete、Natacha Turck、Denis Hochstrasser 和 Jean-Charles Sanchez。人类激酶-蛋白质和激酶-底物网络的比较 激酶-底物相互作用的发生率 与激酶抑制剂的关系 潜在的新治疗方法 激酶相互作用研究如何集中研究。
Biological matter is organized in functional networks of different natures among which kinase–substrate and protein–protein interactions play an important role. Large public data collections allowed us to compile an important corpus of interaction data around human protein kinases. One of the most interesting observations analyzing this network is that coherence in kinase functional activity relies on kinase substrate interactions primarily and not on which protein complexes are formed around them. Further dissecting the two types of interactions at the level of kinase groups (CMGCs, Tyrosine kinases, etc.) we show a prevalence of intra-group interconnectivity, which we can naturally relate to current scenarios of evolution of biological networks. Tracking publication dates we observe high correlation of kinase interaction research focus with general kinase research. We find a similar bias in the targets of kinase inhibitors that feature high redundancy. Finally, intersecting kinase inhibitor specificity with sets of kinases located at specific positions in the kinase network, we propose alternative options for future therapeutic strategies using these compounds. Despite its importance for cellular regulation and the fact that protein kinases feature prominent targets of modern therapeutic approaches, the structure and logic of the global, integrated protein phosphorylation network have not been investigated intensively. To focus on the regulatory skeleton of the phosphorylation network, we contemplated a network consisting of kinases, their substrates, and publicly available physical protein interactions. Analysis of this network at multiple levels allowed establishing a series of interesting properties such as prevalence of kinase substrate interactions as opposed to general protein–protein interactions for establishing a holistic control over kinases activities. Kinases controlling many or a few only other kinases, in addition to non-kinases, were distributed in cellular compartments differently. They were also targeted by kinase inhibitors with distinct success rates. Non-kinases tightly regulated by a large number of kinases were involved in biological processes both specific and shared with their regulators while being preferably localized in the nucleus. Collectively, these observations may provide for a new perspective in the elaboration of pharmacological intervention strategies. We complemented our study of kinase interactions with a perspective of how this type of data is generated in comparison with general research about those enzymes. Namely, what was the temporal evolution of the research community attention for interaction versus non-interaction-based kinase experiments. This article is part of a Special Issue entitled: 20 years of Proteomics in memory of Vitaliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez. Comparison of human kinase–protein and kinase–substrate networks Prevalence of kinase–substrate interactions Relationship with kinase inhibitors Potential new therapeutic approaches How does kinase interaction research focuses its research.
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影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
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影响因子：
14.9
作者：
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通讯作者：
Sullivan M
影响因子：
64.8
作者：
Gavin, AC;Aloy, P;Superti-Furga, G
通讯作者：
Superti-Furga, G
影响因子：
14.9
作者：
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通讯作者：
Diella F