title: Activation of protein kinase CK2 is an early step in the ultraviolet B-mediated increase in interstitial collagenase (matrix metalloproteinase-1; MMP-1) and stromelysin-1 (MMP-3) protein levels in human dermal fibroblasts.
abstract: Enhanced expression of matrix metalloproteinase (MMP)-1/interstitial collagenase and MMP-3/stromelysin-1 in skin fibroblasts and subsequent damage of dermal connective tissue in the context of sun-induced premature aging and skin tumour progression is causally linked to UVB irradiation. Here, we were interested in identifying components of the complex signal-transduction pathway underlying UVB-mediated up-regulation of these delayed UV-responsive genes and focused on components maximally activated early after irradiation. A 2.3-fold increase in protein kinase CK2 activity was measured at 20-40 min after low-dose UVB irradiation (at 10 mJ/cm2) of dermal fibroblasts. This UVB-mediated increase in CK2 activity was abrogated by pharmacological approaches using non-toxic concentrations of the CK2 inhibitor 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB). Preincubation of fibroblasts with DRB prior to UVB irradiation lowered MMP-1 by 49-69% and MMP-3 protein levels by 55-63% compared with UVB-irradiated controls. By contrast, the CK2 inhibitor did not affect the UVB-triggered transcription of MMPs. Furthermore, UVB irradiation of fibroblasts overexpressing a kinase-inactive mutant of CK2 (CK2alpha-K68A-HA) resulted in lowering of the protein levels of MMP-1 by 25% and MMP-3 by 22% compared with irradiated fibroblasts transfected with the vector control. This reduction in MMP protein levels correlated with the transfection efficiency. Taken together, we describe a novel aspect of protein kinase CK2, namely its inducible activity by UVB irradiation, and provide evidence that CK2 is an early mediator of the UVB-dependent up-regulation of MMP-1 and MMP-3 translation, whereas their major tissue inhibitor of matrix metalloproteinase-1 is not affected by CK2.
authors.affiliation: Heinrich-Heine-University of Düsseldorf, Institute for Physiological Chemistry I, Bldg. 22.03, Universitätsstr. 1, 40225 Düsseldorf, Germany. PeterBrenneisen@web.de
authors.forename: Peter
authors.initials: P
authors.lastname: Brenneisen
authors.forename: Meinhard
authors.initials: M
authors.lastname: Wlaschek
authors.forename: Edith
authors.initials: E
authors.lastname: Schwamborn
authors.forename: Lars-Alexander
authors.initials: LA
authors.lastname: Schneider
authors.forename: Wenjian
authors.initials: W
authors.lastname: Ma
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
mesh_terms: D047390:Casein Kinase II; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology / Q000633:toxicity; D004789:Enzyme Activation / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004004:Dichlororibofuranosylbenzimidazole; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1