One-thousand-and-one substrates of protein kinase CK2?
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. Here an updated inventory of 307 CK2 protein substrates is presented. 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. Also numerous are signaling proteins and proteins of viral origin or essential to virus life cycle. In comparison, only a minority of CK2 targets (a dozen or so) are classical metabolic enzymes. 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. 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. The possibility that CK2 phosphosites play some global role, e.g., by destabilizing alpha helices, counteracting caspase cleavage, and generating adhesive motifs, will be discussed.
Meggio
Flavio
F
Dipartimento di Chimica Biologica and Istituto di Neuroscienze del CNR, Università di Padova and Venetian Institute for Molecular Medicine (VIMM), Padova, Italy.
Pinna
Lorenzo A
LA
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D047390:Casein Kinase II; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D013379:Substrate Specificity
D000596:Amino Acids; D020543:Proteome; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases