Evidence for a Role of MSK1 in Transforming Growth Factor-β-mediated Responses through p38α and Smad Signaling Pathways
Smad proteins are central mediators of the transforming growth factor-β (TGF-β) superfamily signaling. The mitogen-activated protein kinase (MAPK) p38 is also one of the downstream targets required for TGF-β-mediated responses. Although the interplay between the p38 and Smad signaling pathways mi...
Saved in:
Published in | The Journal of biological chemistry Vol. 279; no. 29; p. 30474 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
16.07.2004
|
Online Access | Get full text |
Cover
Loading…
Summary: | Smad proteins are central mediators of the transforming growth factor-β (TGF-β) superfamily signaling. The mitogen-activated
protein kinase (MAPK) p38 is also one of the downstream targets required for TGF-β-mediated responses. Although the interplay
between the p38 and Smad signaling pathways might allow cells to display diverse patterns of responses to TGF-β, the mechanism
of this cross-talk is not well established. We report here that inhibition of the p38α isoform suppressed the ability of Smad3
to mediate TGF-β-induced transcriptional responses. The inhibition of p38 activity blocked TGF-β-mediated phosphorylation
of the MSK1 kinase, a substrate of p38 that plays an important role in the remodeling of chromatin. Moreover, we observed
that expression of dominant-interfering mutants of MSK1 blocked the binding of Smad3 to the coactivator p300 in response to
TGF-β signaling. These data reveal a new mechanism whereby the Smad signaling pathway and the p38 cascade are integrated in
the nucleus to activate gene expression. |
---|---|
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M403294200 |