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Regulation of GDF-8 signaling by the p38 MAPK
- Source :
-
Cellular Signalling . Mar2005, Vol. 17 Issue 3, p365-375. 11p. - Publication Year :
- 2005
-
Abstract
- Abstract: Growth differentiation factor-8 (GDF-8), a member of the TGF-β superfamily, is a negative regulator of skeletal muscle growth, which functions through activation of the Smad proteins. We found that GDF-8 can activate the p38 mitogen-activated protein kinase (MAPK) through the TGF-β-activated kinase 1 (TAK1), and this appeared to be independent of Smad signaling. GDF-8-induced transcriptional activation was inhibited by expression of dominant negative MKK6 or treatment with the p38 inhibitor SB203580, while overexpression of wild-type forms of either MKK6 or p38 augmented GDF-8-induced transcriptional activity. In addition, ATF-2, a known transcription factor target of p38, was found to be phosphorylated on GDF-8 stimulation and was detected in a complex with Smad3/Smad4 upon GDF-8 treatment. Furthermore, we found that the p38 MAPK played an important role in GDF-8-induced inhibition of proliferation and upregulation of the cyclin kinase inhibitor p21. Together, these results highlight a functional link between the p38 MAPK and GDF-8-activated Smad pathways, and identify a critical role for the p38 MAPK in GDF-8''s function as a negative regulator of muscle growth. [Copyright &y& Elsevier]
- Subjects :
- *TRANSCRIPTION factors
*PROTEIN kinases
*PROTEINS
*PHOSPHOTRANSFERASES
Subjects
Details
- Language :
- English
- ISSN :
- 08986568
- Volume :
- 17
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Cellular Signalling
- Publication Type :
- Academic Journal
- Accession number :
- 15552990
- Full Text :
- https://doi.org/10.1016/j.cellsig.2004.08.003