Sir Jules Thorn Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
Physiol Rev. 2023 Jul 1;103(3):2231-2269. doi: 10.1152/physrev.00023.2022. Epub 2023 Feb 2.
Salt-inducible kinases (SIKs), which comprise a family of three homologous serine-threonine kinases, were first described for their role in sodium sensing but have since been shown to regulate multiple aspects of physiology. These kinases are activated or deactivated in response to extracellular signals that are cell surface receptor mediated and go on to phosphorylate multiple targets including the transcription cofactors CRTC1-3 and the class IIa histone deacetylases (HDACs). Thus, the SIK family conveys signals about the cellular environment to reprogram transcriptional and posttranscriptional processes in response. In this manner, SIKs have been shown to regulate metabolic responses to feeding/fasting, cell division and oncogenesis, inflammation, immune responses, and most recently, sleep and circadian rhythms. Sleep and circadian rhythms are master regulators of physiology and are exquisitely sensitive to regulation by environmental light and physiological signals such as the need for sleep. Salt-inducible kinases have been shown to be central to the molecular regulation of both these processes. Here, we summarize the molecular mechanisms by which SIKs control these different domains of physiology and highlight where there is mechanistic overlap with sleep/circadian rhythm control.
盐诱导激酶（SIKs），由三个同源丝氨酸-苏氨酸激酶组成，最初因其在钠感应中的作用而被描述，但后来被证明可以调节多种生理功能。这些激酶可被细胞表面受体介导的细胞外信号激活或失活，然后磷酸化多种靶标，包括转录共因子 CRTC1-3 和 IIa 类组蛋白去乙酰化酶（HDACs）。因此，SIK 家族将有关细胞环境的信号传递到转录和转录后过程中，以响应重新编程。通过这种方式，SIK 已被证明可以调节代谢对进食/禁食、细胞分裂和肿瘤发生、炎症、免疫反应的反应，最近还调节睡眠和昼夜节律。睡眠和昼夜节律是生理的主要调节剂，对环境光和生理信号（如睡眠需求）的调节非常敏感。盐诱导激酶被证明是这两个过程的分子调节的核心。在这里，我们总结了 SIK 控制这些不同生理领域的分子机制，并强调了与睡眠/昼夜节律控制的机制重叠之处。
