Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor
Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor
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DOI：
10.1101/gad.12.2.186
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发表时间：
1998-01-15
影响因子：
10.5
通讯作者：
Hemmati-Brivanlou, A
中科院分区：
文献类型：
--
作者：
Hata, A;Lagna, G;Hemmati-Brivanlou, A
骨形态发生蛋白（BMP）受体通过磷酸化Smad 1发出信号，然后与Smad 4结合;该复合物进入细胞核并激活转录。在这里，我们报告存在一种天然的抑制剂，Smad 6，以前报道的JV 15 -1的较长版本。在非洲爪蟾胚胎和哺乳动物细胞中，Smad 6特异性阻断BMP/Smad 1通路的信号传导。Smad 6抑制BMP/Smad 1信号传导，而不干扰受体介导的Smad 1磷酸化。Smad 6特异性地与Smad 4竞争结合受体激活的Smad 1，产生明显无活性的Smad 1-Smad 6复合物。因此，Smad 6选择性地拮抗MBP激活的Smad 1作为Smad 4诱饵。
Bone morphogenetic protein (BMP) receptors signal by phosphorylating Smad1, which then associates with Smad4; this complex moves into the nucleus and activates transcription. Here we report the existence of a natural inhibitor of this process, Smad6, a longer version of the previously reported JV15-1. In Xenopus embryos and in mammalian cells, Smad6 specifically blocks signaling by the BMP/Smad1 pathway. Smad6 inhibits BMP/Smad1 signaling without interfering with receptor-mediated phosphorylation of Smad1. Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes MBP-activated Smad1 by acting as a Smad4 decoy.