Protein kinase CK2 and its role in cellular proliferation, development and pathology

Abstract

Protein kinase CK2 is a pleiotropic, ubiquitous and constitutively active protein kinase that can use both ATP and GTP as phosphoryl donors with specificity for serine/threonine residues in the vicinity of acidic amino acids. Recent results show that the enzyme is involved in transcription, signaling, proliferation and in various steps of development. The tetrameric holoenzyme (α₂β₂) consists of two catalytic α‐subunits and two regulatory β‐subunits. The structure of the catalytic subunit with the fixed positioning of the activation segment in the active conformation through its own aminoterminal region suggests a regulation at the transcriptional level making a regulation by second messengers unlikely. The high conservation of the catalytic subunit from yeast to man and its role in the tetrameric complex supports this notion. The regulatory β‐subunit has been far less conserved throughout evolution. Furthermore the existence of different CK2β‐related proteins together with the observation of deregulated CK2β levels in tumor cells and the reported association of CK2β protein with key proteins in signal transduction, e.g. A‐Raf, Mos, p90^rsk etc. are suggestive for an additional physiological role of CK2β protein beside being the regulatory compound in the tetrameric holoenzyme.