Takase M, Imamura T, Sampath T K, Takeda K, Ichijo H, Miyazono K, Kawabata M
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Biochem Biophys Res Commun. 1998 Mar 6;244(1):26-9. doi: 10.1006/bbrc.1998.8200.
Members of the transforming growth factor-beta (TGF-beta) superfamily transduce signals via Smad proteins. Smad2 and Smad3 mediate TGF-beta signaling, whereas Smad1 and Smad5 transduce bone morphogenetic protein (BMP) signals. Smad4 is a common mediator required for both pathways. Smad6 and Smad7 are recently identified members in the Smad family; they inhibit the signaling activity of the other Smad proteins. Here we show that expression of the Smad6 mRNA is dramatically induced by BMP-2 or osteogenic protein-1 (OP-1)/BMP-7 in various cells. BMP-2 induced expression of Smad7 in one cell type, although much less potently than that of Smad6. Smad6 message was induced by TGF-beta 1 in TGF-beta 1-responsive Mv1Lu cells, but the induction was transient in contrast to the induction by BMPs. These results indicate that Smad6 may form a feedback loop to regulate the signaling activity of BMPs.
转化生长因子-β（TGF-β）超家族的成员通过Smad蛋白传导信号。Smad2和Smad3介导TGF-β信号传导，而Smad1和Smad5传导骨形态发生蛋白（BMP）信号。Smad4是这两条信号通路所必需的共同介导因子。Smad6和Smad7是最近在Smad家族中发现的成员；它们抑制其他Smad蛋白的信号活性。在此我们表明，在各种细胞中，BMP-2或成骨蛋白-1（OP-1）/BMP-7可显著诱导Smad6 mRNA的表达。BMP-2在一种细胞类型中诱导了Smad7的表达，尽管其效力远低于Smad6。在对TGF-β1有反应的Mv1Lu细胞中，TGF-β1可诱导Smad6的表达，但与BMP诱导的情况相比，这种诱导是短暂的。这些结果表明，Smad6可能形成一个反馈环来调节BMP的信号活性。
