PMID- 20717921
OWN - NLM
STAT- MEDLINE
DCOM- 20110328
LR  - 20131121
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 111
IP  - 5
DP  - 2010 Dec 1
TI  - Thapsigargin-induced Ca2+ increase inhibits TGFbeta1-mediated Smad2 transcriptional 
      responses via Ca2+/calmodulin-dependent protein kinase II.
PG  - 1222-30
LID - 10.1002/jcb.22843 [doi]
AB  - Transforming growth factor beta (TGFbeta) signalling plays important roles in a variety 
      of tissues and cell types. Impaired TGFbeta signalling contributes to several 
      pathologies, including cancer, fibrosis as well as neurodegenerative diseases. 
      TGFbeta receptor type I-mediated phosphorylation of Smad2, the formation of the 
      Smad2-Smad4 complex and translocation to the nucleus are critical steps of the 
      TGFbeta signalling pathway. Here, we demonstrate that thapsigargin-mediated increase 
      of intracellular Ca(2+) concentrations inhibited TGFbeta1-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 TGFbeta1 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 TGFbeta signalling in OLI-neu 
      cells was strongly dependent on Ca(2+)-mediated CaMKII activation. In summary, 
      this study clearly shows that the TGFbeta1-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 TGFbeta 
      target genes. These results underline the importance of intracellular Ca(2+) for 
      the regulation of TGFbeta signalling.
CI  - Copyright (c) 2010 Wiley-Liss, Inc.
FAU - Ming, Ming
AU  - Ming M
AD  - Institute of Health Sciences, Shanghai Institutes for Biological Sciences, 
      Chinese Academy of Sciences, and Shanghai Jiao Tong University School of 
      Medicine, Shanghai, PR China.
FAU - Manzini, Ivan
AU  - Manzini I
FAU - Le, Weidong
AU  - Le W
FAU - Krieglstein, Kerstin
AU  - Krieglstein K
FAU - Spittau, Bjorn
AU  - Spittau B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Calcium/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & 
      inhibitors/*metabolism
MH  - Cell Line
MH  - Enzyme Inhibitors
MH  - Humans
MH  - Oligodendroglia/cytology
MH  - Phosphorylation
MH  - *Signal Transduction
MH  - Smad2 Protein/*metabolism
MH  - Thapsigargin/*pharmacology
MH  - *Transcription, Genetic
MH  - Transforming Growth Factor beta1/*genetics/metabolism
EDAT- 2010/08/19 06:00
MHDA- 2011/03/29 06:00
CRDT- 2010/08/19 06:00
PHST- 2010/08/19 06:00 [entrez]
PHST- 2010/08/19 06:00 [pubmed]
PHST- 2011/03/29 06:00 [medline]
AID - 10.1002/jcb.22843 [doi]
PST - ppublish
SO  - J Cell Biochem. 2010 Dec 1;111(5):1222-30. doi: 10.1002/jcb.22843.