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用于调节细胞信号传导的光遗传学控制蛋白激酶

Optogenetically controlled protein kinases for regulation of cellular signaling.

作者信息

Leopold Anna V, Chernov Konstantin G, Verkhusha Vladislav V

机构信息

Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland.

出版信息

Chem Soc Rev. 2018 Apr 3;47(7):2454-2484. doi: 10.1039/c7cs00404d.

Abstract

Protein kinases are involved in the regulation of many cellular processes including cell differentiation, survival, migration, axon guidance and neuronal plasticity. A growing set of optogenetic tools, termed opto-kinases, allows activation and inhibition of different protein kinases with light. The optogenetic regulation enables fast, reversible and non-invasive manipulation of protein kinase activities, complementing traditional methods, such as treatment with growth factors, protein kinase inhibitors or chemical dimerizers. In this review, we summarize the properties of the existing optogenetic tools for controlling tyrosine kinases and serine-threonine kinases. We discuss how the opto-kinases can be applied for studies of spatial and temporal aspects of protein kinase signaling in cells and organisms. We compare approaches for chemical and optogenetic regulation of protein kinase activity and present guidelines for selection of opto-kinases and equipment to control them with light. We also describe strategies to engineer novel opto-kinases on the basis of various photoreceptors.

摘要

蛋白激酶参与许多细胞过程的调控,包括细胞分化、存活、迁移、轴突导向和神经元可塑性。越来越多的光遗传学工具,称为光激酶,可通过光激活和抑制不同的蛋白激酶。光遗传学调控能够对蛋白激酶活性进行快速、可逆和非侵入性操作,补充了传统方法,如使用生长因子、蛋白激酶抑制剂或化学二聚体进行处理。在本综述中,我们总结了用于控制酪氨酸激酶和丝氨酸 - 苏氨酸激酶的现有光遗传学工具的特性。我们讨论了光激酶如何应用于研究细胞和生物体中蛋白激酶信号传导的时空方面。我们比较了蛋白激酶活性的化学调控和光遗传学调控方法,并给出了选择光激酶和用光控制它们的设备的指南。我们还描述了基于各种光感受器设计新型光激酶的策略。

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