Abstract
The early discovery of protein kinase CK2 (an acronym derived from “casein kinase 2”) in 1954 was made possible by its ability to readily phosphorylate in vitro casein. For a while CK2 was suspected to be itself a bona fide casein kinase, because it proved able to re-phosphorylate the same residues which are phosphorylated in native casein. Later, however it was shown that, albeit similar and sometimes overlapping, the consensus sequences of CK2 and the genuine casein kinase isolated from the Golgi apparatus of the lactating mammary gland (G-CK) were definitely distinct (S/T-x-x-E/D/pS vs. S-x-E/pS). While CK2 was recognized as one of the most pleiotropic members of the big family of eukaryotic protein kinases (the so-called kinome) and has been implicated in several global diseases, with special reference to neoplasia, G-CK remained for decades an orphan enzyme, believed to play a dedicated but unexciting role in the biosynthesis of dairy proteins. Even though it became later evident that G-CK is also present in the Golgi apparatus of many tissues and is responsible for the phosphorylation of secreted proteins at S-x-E/pS motifs, its identity remained a mystery until 2012, when it was shown to be indistinguishable from Fam20C, a member of the four-jointed (FJ) atypical kinase family, causative of the Raine syndrome and other biomineralization disorders. Now we know that G-CK/Fam20C is as pleiotropic as CK2, being responsible for the generation of the largest proportion of the phosphosecretome, and, similar to CK2, it may represent a valuable druggable target.
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Acknowledgment
This work was supported by grants from AIRC (Associazione Italiana per la Ricerca sul Cancro) Grant IG10312.
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Tibaldi, E., Arrigoni, G., Cozza, G., Cesaro, L., Pinna, L.A. (2015). “Genuine” Casein Kinase: The False Sister of CK2 That Phosphorylates Secreted Proteins at S-x-E/pS Motifs. In: Ahmed, K., Issinger, OG., Szyszka, R. (eds) Protein Kinase CK2 Cellular Function in Normal and Disease States. Advances in Biochemistry in Health and Disease, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-14544-0_13
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DOI: https://doi.org/10.1007/978-3-319-14544-0_13
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