Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification.
Smad2 and Smad3 have differential sensitivity in relaying TGFβ signaling and inversely regulate early lineage specification.
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Smad2 和 Smad3 在传递 TGF β 信号传导和反向调节早期谱系规范方面具有不同的敏感性
DOI：
10.1038/srep21602
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发表时间：
2016-02-24
影响因子：
4.6
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Liu L;Liu X;Ren X;Tian Y;Chen Z;Xu X;Du Y;Jiang C;Fang Y;Liu Z;Fan B;Zhang Q;Jin G;Yang X;Zhang X
转化生长因子β（transforming growth factor beta，TGFβ）相关信号是调控早期发育事件的重要信号通路之一。Smad 2和Smad 3在结构上相似，并且大多认为它们在介导TGFβ信号中同样重要。在这里，我们表明，Smad 3是一个不敏感的TGFβ转换器相比，Smad 2。Smad 3优先定位于细胞核内，因此与膜信号隔离。鉴于其独特的接头区域，Smad 3在激动剂刺激后与Smad 4寡聚化的能力也受损。Smad 2介导的TGFβ信号转导在上胚层发育和三个胚层的模式化中起关键作用。然而，与信号传导无关的核定位Smad 3对于TGFβ信号传导介导的上胚层特化是不利的，但对于早期神经发育是重要的，这是一个被TGFβ/Smad 2信号传导阻断的事件。Smad 2和Smad 3都与保守的Smads结合元件（SBE）结合，但它们具有非重叠的靶基因结合特异性和不同的转录活性。我们的结论是，Smad 2和Smad 3在传递TGFβ信号方面具有不同的敏感性，并且在调节早期发育事件中具有不同的作用。
The transforming growth factor beta (TGFβ) related signaling is one of the most important signaling pathways regulating early developmental events. Smad2 and Smad3 are structurally similar and it is mostly considered that they are equally important in mediating TGFβ signals. Here, we show that Smad3 is an insensitive TGFβ transducer as compared with Smad2. Smad3 preferentially localizes within the nucleus and is thus sequestered from membrane signaling. The ability of Smad3 in oligomerization with Smad4 upon agonist stimulation is also impaired given its unique linker region. Smad2 mediated TGFβ signaling plays a crucial role in epiblast development and patterning of three germ layers. However, signaling unrelated nuclear localized Smad3 is dispensable for TGFβ signaling-mediated epiblast specification, but important for early neural development, an event blocked by TGFβ/Smad2 signaling. Both Smad2 and Smad3 bind to the conserved Smads binding element (SBE), but they show nonoverlapped target gene binding specificity and differential transcriptional activity. We conclude that Smad2 and Smad3 possess differential sensitivities in relaying TGFβ signaling and have distinct roles in regulating early developmental events.