Protein phosphorylation is the most common reversible post-translational modification in eukaryotes. Humans have over 500 protein kinases, of which more than a dozen are established targets for anticancer drugs. All kinases share a structurally similar catalytic domain, yet each one is uniquely positioned within signaling networks controlling essentially all aspects of cell behavior. Kinases are distinguished from one another based on their modes of regulation and their substrate repertoires. Coupling specific inputs to the proper signaling outputs requires that kinases phosphorylate a limited number of sites to the exclusion of hundreds of thousands of off-target phosphorylation sites. Here, we review recent progress in understanding mechanisms of kinase substrate specificity and how they function to shape cellular signaling networks.

中文翻译：

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归巢：蛋白激酶靶向底物的机制。

蛋白质磷酸化是真核生物中最常见的可逆翻译后修饰。人类拥有500多种蛋白激酶，其中超过12种已确立为抗癌药物的靶标。所有的激酶共享一个结构相似的催化域，但每个激酶都位于信号传导网络中，该信号传导网络实质上控制着细胞行为的所有方面。激酶基于其调节模式和底物库而彼此区分。将特定的输入与适当的信号输出耦合，要求激酶将有限数量的位点磷酸化，以排除成千上万个脱靶的磷酸化位点。在这里，我们回顾了了解激酶底物特异性机制及其如何作用以塑造细胞信号网络的最新进展。