Ecto-protein kinase CK2, the neglected form of CK2

Ecto-protein kinases, including protein kinase CK2 (former name, casein kinase 2), have been the focus of research for more than 30 years. At the beginning of the ecto-kinase research their identification was performed with substrates and inhibitors whose specificity under the current knowledge was rather limited. Since all currently known ecto-kinases, including ecto-CK2, have intracellular counterparts, one has to exclude that an ecto-localization originates from intracellular counterparts after cell damage. Protein kinase CK2 is involved in cellular key processes such as cell cycle progression, inhibition of apoptosis, DNA damage repair, differentiation and many other processes. CK2 is composed of two catalytic CK2 or CK2 subunits and two non-catalytic CK2 subunits. Progress in the ecto-kinase and in particular ecto-CK2 studies was made with the use of transfected tagged CK2 subunits, which allowed to follow their individual transport and localization on the cell surface after transfection. Furthermore, immunofluorescence studies with antibodies against CK2 subunits as well as affinity chromatography with a binding partner of CK2 subunits have improved ecto-kinase research. The use of new and more specific inhibitors as well as of substrates, which do not cross the plasma membrane, have further improved the specificity for ecto-CK2. From the various substrates of ecto-CK2, it can be concluded that ecto-CK2 plays a role in Alzheimer disease, cell adhesion, platelet aggregation, immune response and cellular signalling. New tools and techniques, to study ecto-CK2 activity, are required to identify new substrates and thereby new functional implications for ecto-CK2.