Protein Kinase CK2', More than a Backup of CK2

The serine/threonine protein kinase CK2 is implicated in the regulation of fundamental processes in eukaryotic cells. CK2 consists of two catalytic alpha or alpha' isoforms and two regulatory CK2 beta subunits. These three proteins exist in a free form, bound to other cellular proteins, as tetrameric holoenzymes composed of CK2 alpha(2)/beta(2), CK2 alpha alpha'/beta(2), or CK2 alpha'(2)/beta(2) as well as in higher molecular forms of the tetramers. The catalytic domains of CK2 alpha and CK2 alpha' share a 90% identity. As CK2 alpha contains a unique C-terminal sequence. Both proteins function as protein kinases. These properties raised the question of whether both isoforms are just backups of each other or whether they are regulated differently and may then function in an isoform-specific manner. The present review provides observations that the regulation of both CK2 alpha isoforms is partly different concerning the subcellular localization, post-translational modifications, and aggregation. Up to now, there are only a few isoform-specific cellular binding partners. The expression of both CK2 alpha isoforms seems to vary in different cell lines, in tissues, in the cell cycle, and with differentiation. There are different reports about the expression and the functions of the CK2 alpha isoforms in tumor cells and tissues. In many cases, a cell-type-specific expression and function is known, which raises the question about cell-specific regulators of both isoforms. Another future challenge is the identification or design of CK2 alpha'-specific inhibitors.