Journalartikel

Jahr der Veröffentlichung: 2010

Seiten: 1222-1230

Zeitschrift: Journal of Cellular Biochemistry

Bandnummer: 111

Heftnummer: 5

ISSN: 0730-2312

DOI Link: https://doi.org/10.1002/jcb.22843

Verlag: Wiley

Abstract: 
Transforming growth factor β (TGFβ) signalling plays important roles in a variety of tissues and cell types. Impaired TGFβ signalling contributes to several pathologies, including cancer, fibrosis as well as neurodegenerative diseases. TGFβ receptor type I-mediated phosphorylation of Smad2, the formation of the Smad2-Smad4 complex and translocation to the nucleus are critical steps of the TGFβ signalling pathway. Here, we demonstrate that thapsigargin-mediated increase of intracellular Ca(2+) concentrations inhibited TGFβ1-induced Smad2 transcriptional activity in the oligodendroglial cell line OLI-neu. We provide evidence that thapsigargin treatment dramatically reduced the nuclear translocation of Smad2 after TGFβ1 treatment but had no effect on its phosphorylation at Ser465/467. Moreover, using Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) inhibitors and a constitutively active CaMKII mutant, we provide evidence that the observed inhibition of TGFβ signalling in OLI-neu cells was strongly dependent on Ca(2+)-mediated CaMKII activation. In summary, this study clearly shows that the TGFβ1-induced Smad2 nuclear translocation is negatively regulated by intracellular Ca(2+) in OLI-neu cells and that increased intracellular Ca(2+) concentrations block Smad2-mediated transcription of TGFβ target genes. These results underline the importance of intracellular Ca(2+) for the regulation of TGFβ signalling.

Harvard-Zitierstil: Ming, M., Manzini, I., Le, W., Krieglstein, K. and Spittau, B. (2010) Thapsigargin-induced Ca2+ increase inhibits TGFβ1-mediated Smad2 transcriptional responses via Ca2+/calmodulin-dependent protein kinase II, Journal of Cellular Biochemistry, 111(5), pp. 1222-1230. https://doi.org/10.1002/jcb.22843

APA-Zitierstil: Ming, M., Manzini, I., Le, W., Krieglstein, K., & Spittau, B. (2010). Thapsigargin-induced Ca2+ increase inhibits TGFβ1-mediated Smad2 transcriptional responses via Ca2+/calmodulin-dependent protein kinase II. Journal of Cellular Biochemistry. 111(5), 1222-1230. https://doi.org/10.1002/jcb.22843