Curiously, it was not due to any of the classical protein kinases popular early in the protein phosphorylation era (namely, phosphokinase, PKA, PKG, PKC, etc.) but to two in some way unusual protein kinases, provisionally termed casein kinases or phosvitin kinases, now mostly referred to as CK1 and CK2, whose physiological roles remained enigmatic for a long time (for an historical review, see ref 4) and still are incompletely understood. Such an activity was first detected in rat liver using casein as phosphorylatable substrate and later found ubiquitously in a variety of organisms and tissues.
17, 349–368 (2003)Ī S MENTIONED in a recent historical review on the origins of protein phosphorylation ( 1), the first protein kinase activity was discovered in 1954 by Burnett and Kennedy ( 2) (for an amusing recollection, see E.
One-thousand-and-one substrates of protein kinase CK2? FASEB J. The possibility that CK2 phosphosites play some global role, e.g., by destabilizing α helices, counteracting caspase cleavage, and generating adhesive motifs, will be discussed.-Meggio, F., Pinna, L. Based on this signature, it is predictable that proteins phosphorylated by CK2 are much more numerous than those identified to date, and it is possible that CK2 alone contributes to the generation of the eukaryotic phosphoproteome more so than any other individual protein kinase. An analysis of 308 sites phosphorylated by CK2 highlights the paramount relevance of negatively charged side chains that are (by far) predominant over any other residues at positions n+3 (the most crucial one), n+1, and n+2. In comparison, only a minority of CK2 targets (a dozen or so) are classical metabolic enzymes. Also numerous are signaling proteins and proteins of viral origin or essential to virus life cycle. More than one-third of these are implicated in gene expression and protein synthesis as being either transcriptional factors (60) or effectors of DNA/RNA structure (50) or translational elements. Here an updated inventory of 307 CK2 protein substrates is presented. CK2 (formerly termed “casein kinase 2”) is a ubiquitous, highly pleiotropic and constitutively active Ser/Thr protein kinase whose implication in neoplasia, cell survival, and virus infection is supported by an increasing number of arguments.