THE MULTIPLE ROLES OF SALT-INDUCIBLE KINASES IN REGULATING PHYSIOLOGY

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 physiol-ogy. These kinases are activated or deactivated in response to extracellular signals that are cell surface recep-tor 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.

Automated summary

Salt-inducible kinases (SIKs) are a family of serine-threonine kinases that regulate multiple aspects of physiology. They convey signals about the cellular environment to reprogram transcriptional and posttranscriptional processes. SIKs have been shown to regulate metabolic responses, inflammation, immune responses, and sleep/circadian rhythms. This article summarizes the molecular mechanisms of SIKs in controlling various physiological domains, particularly in the context of sleep and circadian rhythm regulation.