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One-thousand-and-one substrates of protein kinase CK2?
Flavio Meggio1, Lorenzo A Pinna
1Dipartimento di Chimica Biologica and Istituto di Neuroscienze del CNR, Università di Padova and Venetian Institute for Molecular Medicine (VIMM), Padova, Italy.
Abstract:
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.
Insights
Casein kinase 2 (CK2) is a vital protein kinase involved in numerous cellular processes, including gene expression and viral infections. This study identifies 307 CK2 substrates, revealing its broad impact on the phosphoproteome.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Casein kinase 2 (CK2) is a constitutively active Ser/Thr protein kinase.
- CK2 is implicated in various cellular functions, including neoplasia, cell survival, and viral infections.
Purpose of the Study:
- To present an updated inventory of CK2 protein substrates.
- To analyze the characteristics of CK2 phosphorylation sites.
- To discuss the potential global roles of CK2 phosphosites.
Main Methods:
- Literature review and database compilation to identify CK2 substrates.
- Bioinformatic analysis of identified CK2 substrates and phosphorylation sites.
- Comparative analysis of CK2 targets with classical metabolic enzymes.
Main Results:
- An updated inventory identified 307 CK2 protein substrates.
- Over one-third of substrates are involved in gene expression and protein synthesis.
- Analysis of 308 phosphorylation sites revealed a predominance of negatively charged side chains at key positions (n+3, n+1, n+2).
Conclusions:
- CK2 plays a significant role in regulating gene expression, protein synthesis, signaling, and viral life cycles.
- The identified phosphorylation signature suggests a much larger number of CK2 substrates than currently known.
- CK2 may be a major contributor to the eukaryotic phosphoproteome and influence global cellular processes.