Protein kinase CK2: a newcomer in the ‘druggable kinome’

2006 ◽  
Vol 34 (6) ◽  
pp. 1303-1306 ◽  
Author(s):  
M.A. Pagano ◽  
L. Cesaro ◽  
F. Meggio ◽  
L.A. Pinna

The acronym CK2 (derived from the misnomer ‘casein kinase’ 2) denotes one of the most pleiotropic members of the eukaryotic protein kinase superfamily, characterized by an acidic consensus sequence in which a carboxylic acid (or pre-phosphorylated) side chain at position n+3 relative to the target serine/threonine residue plays a crucial role. The latest repertoire of CK2 substrates includes approx. 300 proteins, but the analysis of available phosphopeptide databases from different sources suggests that CK2 alone may be responsible for the generation of a much larger proportion (10–20%) of the eukaryotic phosphoproteome. Although for the time being CK2 is not included among protein kinases whose inhibitors are in clinical practice or in advanced clinical trials, evidence is accumulating that elevated CK2 constitutive activity co-operates to induce a number of pathological conditions, including cancer, infectious diseases, neurodegeneration and cardiovascular pathologies. The development and usage of cell-permeant, selective inhibitors discloses a scenario whereby CK2 plays a global anti-apoptotic role, which under special circumstances may lead to untimely and pathogenic cell survival.

2019 ◽  
Vol 20 (6) ◽  
pp. 547-562 ◽  
Author(s):  
Claudio D'Amore ◽  
Valentina Salizzato ◽  
Christian Borgo ◽  
Luca Cesaro ◽  
Lorenzo A. Pinna ◽  
...  

Substrate pleiotropicity, a very acidic phosphorylation consensus sequence, and an apparent uncontrolled activity, are the main features of CK2, a Ser/Thr protein kinase that is required for a plethora of cell functions. Not surprisingly, CK2 appears to affect cytoskeletal structures and correlated functions such as cell shape, mechanical integrity, cell movement and division. This review outlines our current knowledge of how CK2 regulates cytoskeletal structures, and discusses involved pathways and molecular mechanisms.


2002 ◽  
Vol 362 (2) ◽  
pp. 375-382 ◽  
Author(s):  
Cara J. WESTMARK ◽  
Romi GHOSE ◽  
Paul W. HUBER

Transcription factor IIIA (TFIIIA), isolated from the cytoplasmic 7S ribonucleoprotein complex of Xenopus oocytes, is phosphorylated when incubated with [γ-32P]ATP. This modification is due to a trace kinase activity that remains associated with the factor through several steps of purification. The kinase can use either ATP or GTP, and will phosphorylate casein and phosvitin to the exclusion of TFIIIA. The kinase is reactive with a ten-amino-acid peptide that is a specific substrate for protein kinase CK2 (CK2; formerly casein kinase II). In addition, inhibition of phosphorylation by heparin and stimulation by spermidine indicate that the activity can be ascribed to CK2. Phospho amino acid analysis established that serine is the sole phosphoryl acceptor in TFIIIA. There are four consensus sites for CK2 in TFIIIA; all contain serine residues at the putative site of phosphorylation. TFIIIA immunoprecipitated from oocytes, which were incubated with [32P]orthophosphate, is also phosphorylated exclusively on serine residues. Only the cyanogen bromide fragment, which was derived from the N-terminal end of TFIIIA, is labelled in vivo. A recognition sequence for CK2, located at Ser16 in the β-turn of the first zinc-finger domain, is the only protein kinase consensus sequence present in this peptide. Assays in vitro with site-specific mutants of TFIIIA established that Ser16 is the preferred site of phosphorylation, with some secondary modification at Ser314.


Biochemistry ◽  
2008 ◽  
Vol 47 (32) ◽  
pp. 8317-8325 ◽  
Author(s):  
Giorgia Poletto ◽  
Jordi Vilardell ◽  
Oriano Marin ◽  
Mario A. Pagano ◽  
Giorgio Cozza ◽  
...  

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