title: 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.
authors.affiliation: Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Geb. 44, D-66421 Homburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Schwind
authors.affiliation: Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Geb. 44, D-66421 Homburg, Germany; Fraunhofer-Institut für Biomedizinische Technik IBMT, Ensheimer, Strasse 48, D-66386 St. Ingbert, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Wilhelm
authors.affiliation: Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Geb. 44, D-66421 Homburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kartarius
authors.affiliation: Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Geb. 44, D-66421 Homburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Montenarh
authors.affiliation: Fraunhofer-Institut für Biomedizinische Technik IBMT, Ensheimer, Strasse 48, D-66386 St. Ingbert, Germany.
authors.forename: Erwin
authors.initials: E
authors.lastname: Gorjup
authors.affiliation: Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, Geb. 44, D-66421 Homburg, Germany. Electronic address: claudia.goetz@uks.eu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Götz
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000880:Anthraquinones; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000201:enzymology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology*; D009287:Naphthyridines / Q000494:pharmacology; D047495:PPAR gamma / Q000378:metabolism; D010619:Phenazines
chemical_list: D000880:Anthraquinones; D009287:Naphthyridines; D047495:PPAR gamma; D010619:Phenazines; C543211:1,2,5,8-tetrahydroxy anthraquinone; C555142:silmitasertib; D047390:Casein Kinase II
keywords: Adipogenic differentiation; Kinase inhibitors; Protein kinase CK2; Stem cells