부산대학교 도서관

Transforming growth factor β (TGFβ) 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 TGFβ. Here we show that another p38 MAPK inhibitor, PD169316, abrogates signaling initiated by both TGFβ and Activin A, but not bone morphogenetic protein (BMP) 4. Inhibition of TGFβ signaling is dose dependent and results in reduced Smad2 and Smad3 phosphorylation, nuclear translocation, and up-regulation of the TGFβ target gene Smad7. Reduced TGFβ 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 TGFβ/Smad signaling. Our results show that use of PD169316 at 5 μM or higher can block TGFβ signaling activity and thus caution must be used when attributing cellular activities exclusively to p38 MAPK signaling when these inhibitors are used experimentally. [Copyright &y& Elsevier]