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

Journal Article · Fri Mar 23 00:00:00 EDT 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.01.113· OSTI ID:20979849

Dziembowska, Magdalena ^[1]; Danilkiewicz, Malgorzata ^[1]; Wesolowska, Aleksandra ^[1]; Zupanska, Agata ^[1]; Chouaib, Salem ^[2]; Kaminska, Bozena ^[1]

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1. Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093 Warsaw (Poland)
2. Laboratoire d'Immunologie des Tumeurs Humaines, INSERM U753, Institut Gustave Roussy, Villejuif (France)

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-{beta}1 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-{beta}1-induced signalling.

• OSTI ID: 20979849
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 354; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL PROLIFERATION
GLIOMAS
GROWTH FACTORS
INHIBITION
PHOSPHORUS 38
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RECEPTORS
TRANSCRIPTION FACTORS