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Biochem Biophys Res Commun. 2007 Mar 23;354(4):1101-6. Epub 2007 Jan 29.

Cross-talk between Smad and p38 MAPK signalling in transforming growth factor beta signal transduction in human glioblastoma cells.

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  • 1Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.

Abstract

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine involved in the regulation of cell proliferation, differentiation, and survival. Malignant tumour cells often do not respond to TGF-beta by growth inhibition, but retain responsiveness to cytokine in regulating extracellular matrix deposition, cell adhesion, and migration. We demonstrated that TGF-beta1 does not affect viability or proliferation of human glioblastoma T98G, but increases transcriptional responses exemplified by induction of MMP-9 expression. TGF-beta receptors were functional in T98G glioblastoma cells leading to SMAD3/SMAD4 nuclear translocation and activation of SMAD-dependent promoter. In parallel, a selective activation of p38 MAPK, and phosphorylation of its substrates: ATF2 and c-Jun proteins were followed by a transient activation of AP-1 transcription factor. Surprisingly, an inhibition of p38 MAPK with a specific inhibitor, SB202190, abolished TGF-inducible activation of Smad-dependent promoter and decreased Smad2 phosphorylation. It suggests an unexpected interaction between Smad and p38 MAPK pathways in TGF-beta1-induced signalling.

PMID:
17276399
[PubMed - indexed for MEDLINE]
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