Smad6 inhibits signalling by the TGF-beta superfamily
Smad6 inhibits signalling by the TGF-beta superfamily
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DOI：
10.1038/39355
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发表时间：
1997-10-09
期刊：
影响因子：
64.8
通讯作者：
Miyazono, K
中科院分区：
文献类型：
--
作者：
Imamura, T;Takase, M;Miyazono, K
SMBD蛋白（1）已被鉴定为TGF-β超家族的信号传导介质，其参与一系列生物活性，包括细胞生长、形态发生、发育和免疫应答（2，3）。Smad 1、Smad 2、Smad 3和Smad 5是来自骨形态发生蛋白的配体特异性Smad 1和Smad 5信号（4-7），Smad 2和Smad 3通过TGF-β和激活素介导信号传导（8，9），而Smad 4作为常见的信号传导组分（10）。例如，Smad 2在配体结合后被TGF-β I型受体磷酸化，与Smad 4形成异聚体，然后易位到细胞核中，在那里它激活转录（10，11）。在这里，我们报告的Smad 6在小鼠中的分离。Smad 6在结构上与其他SMAD蛋白质完全不同，并且与I型受体形成稳定的缔合。Smad 6干扰Smad 2的磷酸化和随后与Smad 4的异聚化，但不抑制Smad 3的活性，Smad 6还抑制由骨形态发生蛋白IB型受体诱导的Smad 1的磷酸化。这些数据表明TGF-β超家族的信号受到SMAD家族成员的正向和负向调节。
SMBD proteins(1) have been identified as signalling mediators of the TGF-beta superfamily, which is involved in a range of biological activities including cell growth, morphogenesis, development and immune responses(2,3). Smad1, Smad2, Smad3 and Smad5 are ligand-specific Smad1 and Smad5 transduce signals from bone morphogenetic proteins(4-7), and Smad2 and Smad3 mediate signalling by TGF-beta and activin(8,9), whereas Smad4 acts as a common signalling component(10). For example, Smad2 is phosphorylated by the TGF-beta type I receptor upon ligand binding, forms a heteromer with Smad4 and then translocates into the nucleus where it activates transcription(10,11). Here we report the isolation of Smad6 in the mouse. Smad6 is quite different in structure from the other SMAD proteins, and forms stable associations with type I receptors. Smad6 interferes with the phosphorylation of Smad2 and the subsequent heteromerization with Smad4, but does not inhibit the activity of Smad3, Smad6 also inhibits the phosphorylation of Smad1 that is induced by the bone morphogenetic protein type IB receptor. These data indicate that signals of the TGF-beta superfamily are regulated both positively and negatively by members of the SMAD family.