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

Abstract

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.

Different Persistence of the Cellular Effects Promoted by Protein Kinase CK2 Inhibitors CX-4945 and TDB

“…However, other possibilities should be also taken into account. In accordance with our results, Schwind and colleagues have recently published a paper [ 23 ] where the inhibition by CX-4945 and its effects on stem cell differentiation were found to decrease from 24 h to 72 h. Since in that case the inhibitor was maintained in contact with cells for all the length of the experiment, the result would indicate that its effective concentration decreased, and this could be due to several causes, such as compound extrusion, subcellular redistribution, or metabolic inactivation.…”

Protein kinase CK2 in development and differentiation

“…After day six of differentiation, inhibition of CK2 activity demonstrated no effect on the differentiation process. Very similar results were reported for the adipogenic differentiation of human mesenchymal stem cells (62). In this case it was, however, shown that mesenchymal stem cells respond differently to the type of inhibitor for the CK2 enzyme activity.…”

Protein Kinase CK2 Regulates Leukocyte-Endothelial Cell Interactions during Ischemia and Reperfusion in Striated Skin Muscle

“…For instance, Hu and Wieloch [31] found that distinct brain regions are protected by an increased CK2 activity against ischemic cell death. These findings are in line with the well-known antiapoptotic function of CK2 [32]. Moreover, Mottet et al [33] reported that CK2 positively regulates hypoxia-inducible factor 1 activity in tumor cells, mediating their adaptation to hypoxia.…”