Casein Kinases: An Atypical Class of Ubiquitous and Pleiotropic Protein Kinases

Summary

The term casein kinase applies to a small group of Ser/Thr specific protein kinases that by far prefer casein over histones as in vitro substrates. While however genuine casein kinases specifically expressed in the lactating mammary gland are actually responsible for the biosynthetic phosphorylation of casein fractions, two quite unrelated types of ubiquitous casein kinases, conventionally termed CK1 and CK2, are committed with the phosphorylation and regulation of a variety of protein targets involved in several cellular functions, with special reference to gene expression and signal transduction. CK2 is in particular a growth related protein kinase which, despite its heterotetrameric structure composed of two catalytic (α and/or α′) and two non catalytic (β) subunits, is spontaneously active and apparently lacks any acute control mechanism. Its canonical consensus sequence is Ser(Thr)-Xaa-Xaa-Glu(Asp, SerP, TyrP) but it can be surrogated in peptide substrates by atypical motif(s) generated by previously phosphorylated serines, notably (SerP)-SerP-Ser-SerP. CK2 specificity moreover can be deeply altered by polycationic effectors, like polylysine, and by the subunit composition of the enzyme, as disclosed by using its recombinant catalytic subunit (rα) and the reconstituted holoenzyme (rα₂rβ₂). It is proposed that such a multifarious and flexible specificity could provide CK2 with a sui generis mechanism of regulation.