Structural basis of the constitutive activity of protein kinase CK2

Abstract

Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. In mammals, there are two paralog catalytic subunits, that is, CK2α (A1) and CK2α' (A2), and one CK2β dimer, which together form the heterotetrameric holoenzyme. The presence of full functioning CK2α and CK2β subunits are absolutely mandatory for embryonic development. Total knockouts are lethal. The CK2α' paralog seems to be an exception inasmuch as a total knockout only leads to sterility in male mice. The catalytic subunits are distantly related to the CMGC subfamily of protein kinases, such as the cyclin-dependent kinases (CDKs). There are some peculiarities associated with protein kinase CK2, which are not found with most of the other protein kinases: the enzyme is constitutively active, it can use ATP and GTP as phosphoryl donors, and it is found elevated in most tumors investigated and rapidly proliferating tissues. In this review, we explain (i) its constitutive activity at the intramolecular level, and (ii) come forward with a model how this protein kinase could be regulated in cells by a mechanism involving intermolecular interactions.