Protein kinase CK2 is necessary for the adipogenic differentiation of human mesenchymal stem cells

• Published in: Biochimica et biophysica acta 2015-10, Vol.1853 (10), p.2207-2216
• Main Authors: Schwind, Lisa, Wilhelm, Nadine, Kartarius, Sabine, Montenarh, Mathias, Gorjup, Erwin, Götz, Claudia
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus - drug effects; Active Transport, Cell Nucleus - physiology; Adipogenesis - drug effects; Adipogenesis - physiology; Adipogenic differentiation; Animals; Anthraquinones; Casein Kinase II - antagonists & inhibitors; Casein Kinase II - metabolism; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Nucleus - enzymology; Cell Proliferation - drug effects; Cell Proliferation - physiology; Female; Humans; Kinase inhibitors; Male; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - enzymology; Naphthyridines - pharmacology; PPAR gamma - metabolism; Protein kinase CK2; Stem cells
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2015.05.023

CK2 is a serine/threonine protein kinase, which is so important for many aspects of cellular regulation that life without CK2 is impossible. Here, we analysed CK2 during adipogenic differentiation of human mesenchymal stem cells (hMSCs). With progress of the differentiation CK2 protein level and the kinase activity decreased. Whereas CK2α remained in the nucleus during differentiation, the localization of CK2β showed a dynamic shuttling in the course of differentiation. Over the last years a large number of inhibitors of CK2 kinase activity were generated with the idea to use them in cancer therapy. Our results show that two highly specific inhibitors of CK2, CX-4945 and quinalizarin, reduced its kinase activity in proliferating hMSC with a similar efficiency. CK2 inhibition by quinalizarin resulted in nearly complete inhibition of differentiation whereas, in the presence of CX-4945, differentiation proceeded similar to the controls. In this case, differentiation was accompanied by the loss of CX-4945 inhibitory function. By analysing the subcellular localization of PPARγ2, we found a shift from a nuclear localization at the beginning of differentiation to a more cytoplasmic localization in the presence of quinalizarin. Our data further show for the first time that a certain level of CK2 kinase activity is required for adipogenic stem cell differentiation and that inhibition of CK2 resulted in an altered localization of PPARγ2, an early regulator of differentiation. [Display omitted] •Protein kinase CK2 is down-regulated during the differentiation of hMSC to adipocytes.•Inhibition of CK2 activity in hMSC interferes with the differentiation to adipocytes.•CK2 inhibitors differ in their inhibition efficiency in differentiating hMSC.•A particular level of CK2 kinase activity is necessary for the differentiation of human stem cells.