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蛋白激酶CK2与离子通道(综述)

Protein kinase CK2 and ion channels (Review).

作者信息

Montenarh Mathias, Götz Claudia

机构信息

Medical Biochemistry and Molecular Biology, Saarland University, D-66424 Homburg, Saarland, Germany.

出版信息

Biomed Rep. 2020 Dec;13(6):55. doi: 10.3892/br.2020.1362. Epub 2020 Sep 30.

Abstract

Protein kinase CK2 appears as a tetramer or higher molecular weight oligomer composed of catalytic CK2α, CK2α' subunits and non-catalytic regulatory CK2β subunits or as individual subunits. It is implicated in a variety of different regulatory processes, such as Akt signalling, splicing and DNA repair within eukaryotic cells. The present review evaluates the influence of CK2 on ion channels in the plasma membrane. CK2 phosphorylates platform proteins such as calmodulin and ankyrin G, which bind to channel proteins for a physiological transport to and positioning into the membrane. In addition, CK2 directly phosphorylates a variety of channel proteins directly to regulate opening and closing of the channels. Thus, modulation of CK2 activities by specific inhibitors, by siRNA technology or by CRISPR/Cas technology has an influence on intracellular ion concentrations and thereby on cellular signalling. The physiological regulation of the intracellular ion concentration is important for cell survival and correct intracellular signalling. Disturbance of this regulation results in a variety of different diseases including epilepsy, heart failure, cystic fibrosis and diabetes. Therefore, these effects should be considered when using CK2 inhibition as a treatment option for cancer.

摘要

蛋白激酶CK2表现为一种四聚体或由催化性CK2α、CK2α'亚基和非催化性调节性CK2β亚基组成的更高分子量寡聚体,也可以是单个亚基。它参与多种不同的调节过程,如真核细胞内的Akt信号传导、剪接和DNA修复。本综述评估了CK2对质膜中离子通道的影响。CK2使诸如钙调蛋白和锚蛋白G等平台蛋白磷酸化,这些蛋白与通道蛋白结合以进行生理转运并定位到膜中。此外,CK2直接使多种通道蛋白磷酸化以调节通道的开闭。因此,通过特异性抑制剂、siRNA技术或CRISPR/Cas技术对CK2活性进行调节会影响细胞内离子浓度,进而影响细胞信号传导。细胞内离子浓度的生理调节对细胞存活和正确的细胞内信号传导很重要。这种调节的紊乱会导致包括癫痫、心力衰竭、囊性纤维化和糖尿病在内的多种不同疾病。因此,在将CK2抑制作为癌症治疗选择时应考虑这些影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35e3/7560519/cc4fcac6308f/br-13-06-01362-g00.jpg

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