Glycogen synthase kinase (GSK)-3α/β and the double-stranded RNA-dependent kinase PKR are two sentinel kinases that carry-out multiple similar yet distinct functions in both the cytosol and the nucleus. While these kinases belong to separate signal transduction cascades, they demonstrate an uncanny propensity to regulate many of the same proteins either through direct phosphorylation or by altering transcription/translation, including: c-MYC, NF-κB, p53 and TAU, as well as each another. A significant number of studies centered on the GSK3 kinases have led to the identification of the GSK3 interactome and a number of substrates, which link GSK3 activity to metabolic control, translation, RNA splicing, ribosome biogenesis, cellular division, DNA repair and stress/inflammatory signaling. Interestingly, many of these same pathways and processes are controlled by PKR, but unlike the GSK3 kinases, a clear picture of proteins interacting with PKR and a complete listing of its substrates is still missing. In this review, we take a detailed look at what is known about the PKR and GSK3 kinases, how these kinases interact to influence common cellular processes (innate immunity, alternative splicing, translation, glucose metabolism) and how aberrant activation of these kinases leads to diseases such as Alzheimer's disease (AD), diabetes mellitus (DM) and cancer.

糖原合酶激酶（GSK）-3α/β和双链RNA依赖性激酶PKR是两个前哨蛋白激酶，在细胞质和细胞核中都执行多种相似但截然不同的功能。尽管这些激酶属于单独的信号转导级联，但它们显示出通过直接磷酸化或通过改变转录/翻译来调节许多相同蛋白质的异常倾向，包括：c-MYC，NF-κB，p53和TAU，以及其他每一个。大量以GSK3激酶为中心的研究已鉴定出GSK3相互作用组和许多底物，这些底物将GSK3活性与代谢控制，翻译，RNA剪接，核糖体生物发生，细胞分裂，DNA修复和应激/炎症联系在一起信号。有趣的是 这些相同的途径和过程中有许多是受PKR控制的，但与GSK3激酶不同，与PKR相互作用的蛋白质的清晰图景及其底物的完整列表仍不存在。在这篇综述中，我们详细了解PKR和GSK3激酶的知识，这些激酶如何相互作用以影响常见的细胞过程（先天免疫，选择性剪接，翻译，葡萄糖代谢）以及这些激酶的异常激活如何导致阿尔茨海默氏病（AD），糖尿病（DM）和癌症等疾病。