Protein kinase CK2 and ion channels (Review)

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.

Keywords: ion channels; phosphorylation; protein kinase CK2; protein- protein interaction; review.

Figure 1

Influence of CK2 phosphorylation on binding of channel proteins to (A) ankyrin G or (B) calmodulin. Green arrows represent phosphorylation and interaction. Blue lines indicate an interaction. P, phosphate; CK2, casein kinase 2; SK, small conductance; KCNQ2, potassium voltage-gated channel subfamily Q member 2; Nav, sodium voltage-gated channels.