PDF(Pubmed)
Abstract：
Regarded as constitutively active enzymes, known to participate in many, diverse biological processes, the intracellular regulation bestowed on the CK1 family of serine/threonine protein kinases is critically important, yet poorly understood. Here, we provide an overview of the known CK1-dependent cellular functions and review the emerging roles of CK1-regulating proteins in these processes. We go on to discuss the advances, limitations and pitfalls that CK1 researchers encounter when attempting to define relationships between CK1 isoforms and their substrates, and the challenges associated with ascertaining the correct physiological CK1 isoform for the substrate of interest. With increasing interest in CK1 isoforms as therapeutic targets, methods of selectively inhibiting CK1 isoform-specific processes is warranted, yet challenging to achieve given their participation in such a vast plethora of signalling pathways. Here, we discuss how one might shut down CK1-specific processes, without impacting other aspects of CK1 biology.
摘要：
被认为是组成型活性酶，已知参与许多，不同的生物过程，赋予丝氨酸/苏氨酸蛋白激酶CK1家族的细胞内调节至关重要，但却知之甚少。这里,我们提供了已知的CK1依赖性细胞功能的概述，并回顾了CK1调节蛋白在这些过程中的新兴作用。我们继续讨论进展，CK1研究人员在试图定义CK1同工型及其底物之间的关系时遇到的局限性和陷阱，以及与确定目标底物的正确生理CK1同种型相关的挑战。随着对CK1亚型作为治疗靶标的兴趣日益增加，选择性抑制CK1同工型特异性过程的方法是必要的，然而，鉴于他们参与如此庞大的信号通路，实现这一目标具有挑战性。这里,我们讨论了如何关闭特定于CK1的进程，不影响CK1生物学的其他方面。
