Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B cells
Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activin-mediated growth arrest and apoptosis in B cells
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DOI：
10.1074/jbc.274.19.13637
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发表时间：
1999-05-07
影响因子：
4.8
通讯作者：
Nishihara, T
中科院分区：
文献类型：
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作者：
Ishisaki, A;Yamato, K;Nishihara, T
Smad 6和Smad 7阻止转化生长因子-β家族中信号转导Smad蛋白的配体诱导的活化。在这里，我们证明Smad 6和Smad 7都是人骨形态发生蛋白-2（hBMP-2）诱导的拮抗剂，可以抑制hBMP-2诱导的小鼠B细胞杂交瘤HS-72细胞生长停滞和细胞凋亡。此外，我们证实了Smad 6和Smad 7的异位表达抑制hBMP-2诱导的Smad 1/Smad 5磷酸化。我们以前报道过Smad 7是激活素A诱导的HS-72细胞生长停滞和凋亡的拮抗剂。有趣的是，尽管激活素A诱导HS-72细胞中Smad 6的mRNA表达，但Smad 6对激活素A诱导的生长停滞和凋亡没有拮抗作用。此外，我们发现Smad 7的异位表达抑制了激活素A诱导的HS-72细胞中Smad 2的磷酸化，而不是Smad 6。因此，Smad 6和Smad 7在B谱系细胞中的骨形态发生蛋白-2和激活素A介导的信号传导中表现出不同的抑制作用。
Smad6 and Smad7 prevent ligand-induced activation of signal-transducing Smad proteins in the transforming growth factor-p family. Here we demonstrate that both Smad6 and Smad7 are human bone morphogenetic protein-2 (hBMP-2)-inducible antagonists of hBMP-2-induced growth arrest and apoptosis in mouse B cell hybridoma HS-72 cells. Moreover, we confirmed that the ectopic expressions of Smad6 and Smad7 inhibited the hBMP-2-induced Smad1/Smad5 phosphorylation. We previously reported that Smad7 is an activin A-inducible antagonist of activin A-induced growth arrest and apoptosis in HS-72 cells. Interestingly, although mRNA expression of Smad6 was induced by activin A in HS-72 cells, Smad6 showed no antagonistic effect on activin A-induced growth arrest and apoptosis, Moreover, we found that the ectopic expression of Smad7, but not Smad6, inhibited the activin A-induced Smad2 phosphorylation in HS-72 cells. Thus, Smad6 and Smad7 exhibit differential inhibitory effects in bone morphogenetic protein-2- and activin A-mediated signaling in B lineage cells.