The p38 MAPK inhibitor, PD169316, inhibits transforming growth factor β-induced Smad signaling in human ovarian cancer cells
The p38 MAPK inhibitor, PD169316, inhibits transforming growth factor β-induced Smad signaling in human ovarian cancer cells
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DOI：
10.1016/j.bbrc.2003.09.021
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发表时间：
2003-10-17
影响因子：
3.1
通讯作者：
Nachtigal, MW
中科院分区：
文献类型：
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作者：
Fu, YX;O'Connor, LM;Nachtigal, MW
转化生长因子P(TGFbeta)可通过多种不依赖Smad的途径传递信号，包括p38MAPK途径。最近的工作表明，p38 MAPK的抑制剂，如SB203580和SB202190，可以抑制TGFbeta诱导的信号转导。在这里，我们发现另一种p38 MAPK抑制剂，PD169316，可以同时取消由TGFbeta和激活素A启动的信号转导，而不是骨形态发生蛋白(BMP)4。抑制TGFbeta信号转导是剂量依赖的，并导致Smad2和Smad3磷酸化减少。核易位，以及TGFβ靶基因Smad7的上调。由于以p38MAPK为主的阴性形式阻断p38MAPK活性对TGFbeta/Smad信号没有影响，因此TGFbeta信号的减少并不是由于p38MAPK活性的丧失所致。我们的结果表明，在5微米或更高的浓度下使用PD 169316可以阻断转化生长因子β信号的活性，因此在实验中使用这些抑制剂时，当将细胞活动专门归因于p38MAPK信号时必须谨慎。(C)2003 Elsevier Inc.保留所有权利。
Transforming growth factor P (TGFbeta) can signal through a variety of Smad-independent pathways, including the p38 MAPK pathway. Recent work has shown that inhibitors of p38 MAPK, such as SB203580 and SB202190, can inhibit signaling induced by TGFbeta. Here we show that another p38 MAPK inhibitor, PD169316, abrogates signaling initiated by both TGFbeta and Activin A, but not bone morphogenetic protein (BMP) 4. Inhibition of TGFbeta signaling is dose dependent and results in reduced Smad2 and Smad3 phosphorylation. nuclear translocation, and up-regulation of the TGFbeta target gene Smad7. Reduced TGFbeta signaling is not due to abrogation of p38 MAPK activity, since blocking p38 MAPK activity with a dominant negative form of p38 MAPK has no effect on TGFbeta/Smad signaling. Our results show that use of PD 169316 at 5 muM or higher can block TGFbeta signaling activity and thus caution must be used when attributing cellular activities exclusively to p38 MAPK signaling when these inhibitors are used experimentally. (C) 2003 Elsevier Inc. All rights reserved.