Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential.

Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential.
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DOI:
10.1016/j.tem.2018.08.004
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发表时间:
2018-10
期刊:
Trends in endocrinology and metabolism: TEM
影响因子:
--
通讯作者:
Kronenberg HM
Kronenberg HM
中科院分区:
其他
文献类型:
--
作者:
Wein MN;Foretz M;Fisher DE;Xavier RJ;Kronenberg HM

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盐诱导激酶是AMPK家族激酶的一个亚家族。最初命名是因为SIK1(该激酶家族的创始成员)的表达受肾上腺饮食盐摄入量的调节,现在很明显,这些激酶的主要生物学作用是控制细胞外信号的基因表达,从而增加细胞内cAMP水平。在这里,我们将回顾四个cAMP信号如何影响SIK细胞功能的生理相关例子。通过关注camp介导的SIK在肠髓细胞、骨、肝和皮肤中的调节,我们将重点介绍G蛋白偶联受体信号转导的最新进展。关于盐诱导激酶在GPCR信号传导中的作用的新知识导致了新型小分子SIK抑制剂的治疗应用。
Salt inducible kinases represent a subfamily of AMPK family kinases. Initially named because SIK1 (the founding member of this kinase family) expression is regulated by dietary salt intake in the adrenal gland, it is now apparent that a major biological role of these kinases is to control gene expression in response extracellular cues that increase intracellular levels of cAMP. Here, we will review four physiologically-relevant examples of how cAMP signaling impinges upon SIK cellular function. By focusing on examples of cAMP-mediated SIK regulation in gut myeloid cells, bone, liver, and skin, we will highlight recent advances in G protein coupled receptor signal transduction. New knowledge regarding the role of salt inducible kinases in GPCR signaling has led to therapeutic applications of novel small molecule SIK inhibitors.
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