Casein kinase: the triple meaning of a misnomer

Abstract

The term 'casein kinase' has been widely used for decades to denote protein kinases sharing the ability to readily phosphorylate casein in vitro. These fall into three main classes: two of them, later renamed as protein kinases CK1 (casein kinase 1, also known as CKI) and CK2 (also known as CKII), are pleiotropic members of the kinome functionally unrelated to casein, whereas G-CK, or genuine casein kinase, responsible for the phosphorylation of casein in the Golgi apparatus of the lactating mammary gland, has only been identified recently with Fam20C [family with sequence similarity 20C; also known as DMP-4 (dentin matrix protein-4)], a member of the four-jointed family of atypical protein kinases, being responsible for the phosphorylation of many secreted proteins. In hindsight, therefore, the term 'casein kinase' is misleading in every instance; in the case of CK1 and CK2, it is because casein is not a physiological substrate, and in the case of G-CK/Fam20C/DMP-4, it is because casein is just one out of a plethora of its targets, and a rather marginal one at that. Strikingly, casein kinases altogether, albeit representing a minimal proportion of the whole kinome, appear to be responsible for the generation of up to 40-50% of non-redundant phosphosites currently retrieved in human phosphopeptides database. In the present review, a short historical explanation will be provided accounting for the usage of the same misnomer to denote three unrelated classes of protein kinases, together with an update of our current knowledge of these pleiotropic enzymes, sharing the same misnomer while playing very distinct biological roles.

Stability of Structured Kaposi's Sarcoma-Associated Herpesvirus ORF57 Protein Is Regulated by Protein Phosphorylation and Homodimerization

“…Given that IDRs bear predominant sites of protein posttranslational modification (45), we were able to correctly predict the majority of ORF57, ICP27, UL69, and EB2 phosphorylation sites (data not shown) by using DISPHOS, a disorder-enhanced phosphorylation sites predictor. Although CKII is a ubiquitous kinase responsible for phosphorylation of approximately a quarter of all phosphorylation sites identified in eukaryotic phosphoproteomes (64) and is a common kinase in phosphorylation of serine/threonine residues in ORF57 and its homologues, another kinase(s) may phosphorylate ORF57 at S95 and S97. In this study, recombinant ORF57 purified from Sf21 cells could be phosphorylated by itself in the presence of [␥-32 P]ATP.…”

Enzyme Activities of the Ceramide Synthases CERS2–6 Are Regulated by Phosphorylation in the C-terminal Region

“…3). CK2 is a highly pleiotropic, constitutively active Ser/Thr kinase that is responsible for catalyzing almost one-fourth of the known phosphoproteome (33). The expression level and activity of CK2 are elevated in many cancers originating from diverse tissues (40).…”

“…Most of the potentially phosphorylated serine residues match the consensus motif for phosphorylation by CK2 (i.e. (S/T)XX(D/E), where X stands for any amino acid, S for serine, T for threonine, D for aspartate, and E for glutamate) (33) (Fig. 1).…”

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

“…43,45,46 Here we selected EGCG on the basis of its ability to modulate the activity of one particular Ser/Thr kinase, CSNK2, a "master protein kinase" involved in multiple cellular processes. 59 CSNK2 activity is reportedly involved in the proteolytic degradation of F508del-CFTR 50,60 in a self-supported loop where CSNK2 ultimately promotes fragmentation/degradation of CFTR such that the resulting CFTR fragments allosterically activate CSNK2. 61 Thus, targeting CSNK2 could represent an alternative approach to improve F508del-CFTR stability, in accord with the finding that a highly selective inhibitor of CSNK2 mimicked the capacity of EGCG to sustain F508del-CFTR function beyond cysteamine washout.…”