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Strategies for Engineering and Rewiring Kinase Regulation.
Trends in Biochemical Sciences ( IF 11.6 ) Pub Date : 2019-12-19 , DOI: 10.1016/j.tibs.2019.11.005
James W McCormick 1 , David Pincus 2 , Orna Resnekov 3 , Kimberly A Reynolds 1
Affiliation  

Eukaryotic protein kinases (EPKs) catalyze the transfer of a phosphate group onto another protein in response to appropriate regulatory cues. In doing so, they provide a primary means for cellular information transfer. Consequently, EPKs play crucial roles in cell differentiation and cell-cycle progression, and kinase dysregulation is associated with numerous disease phenotypes including cancer. Nonnative cues for synthetically regulating kinases are thus much sought after, both for dissecting cell signaling pathways and for pharmaceutical development. In recent years advances in protein engineering and sequence analysis have led to new approaches for manipulating kinase activity, localization, and in some instances specificity. These tools have revealed fundamental principles of intracellular signaling and suggest paths forward for the design of therapeutic allosteric kinase regulators.

中文翻译:

工程和重新布线激酶调节策略。

真核蛋白激酶(EPK)响应适当的调控信号,催化磷酸基团转移到另一种蛋白上。这样做,它们提供了用于蜂窝信息传输的主要手段。因此,EPK在细胞分化和细胞周期进程中起关键作用,并且激酶失调与包括癌症在内的多种疾病表型有关。因此,无论是用于解剖细胞信号传导途径还是用于药物开发,都非常需要用于合成调节激酶的非天然提示。近年来,蛋白质工程和序列分析的进步导致了操纵激酶活性,定位以及某些情况下特异性的新方法。
更新日期:2019-12-20
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