The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling.
The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling.
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DOI：
10.1083/jcb.200106023
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发表时间：
2001-12-10
期刊：
影响因子：
--
通讯作者：
Miyazono K
中科院分区：
文献类型：
--
作者：
Hanyu A;Ishidou Y;Ebisawa T;Shimanuki T;Imamura T;Miyazono K
抑制性Smads（I-Smads）通过转化生长因子-β（TGF-β）超家族的细胞因子抑制信号传导。I-Smads具有保守的羧基末端Mad同源2（MH 2）结构域，而其氨基末端区域（N结构域）的氨基酸序列与其他Smads的氨基酸序列高度不同。在哺乳动物中的两种不同的I-Smads中，Smad 7抑制TGF-β和骨形态发生蛋白（BMP）的信号传导，而Smad 6在抑制TGF-β信号传导方面效果较差。使用Smad 6和Smad 7的缺失突变体和嵌合体的分析揭示，MH 2结构域负责I-Smads抑制TGF-β和BMP信号传导，但Smad 6和Smad 7的分离的MH 2结构域在抑制TGF-β信号传导方面不如全长Smad 7有效。I-Smads的N结构域决定了这些分子的亚细胞定位。与含有Smad 6的N结构域的嵌合体相比，含有Smad 7的N结构域的嵌合体与TGF-β I型受体（TβR-I）的相互作用更有效，并且在抑制TGF-β信号传导方面更有效。分离的Smad 7的N结构域与Smad 7的MH 2结构域物理相互作用，并通过促进与TGF-β受体的相互作用增强后者的抑制活性。因此，Smad 7的N结构域在TGF-β信号传导的特异性抑制中起重要作用。
Inhibitory Smads (I-Smads) repress signaling by cytokines of the transforming growth factor-β (TGF-β) superfamily. I-Smads have conserved carboxy-terminal Mad homology 2 (MH2) domains, whereas the amino acid sequences of their amino-terminal regions (N domains) are highly divergent from those of other Smads. Of the two different I-Smads in mammals, Smad7 inhibited signaling by both TGF-β and bone morphogenetic proteins (BMPs), whereas Smad6 was less effective in inhibiting TGF-β signaling. Analyses using deletion mutants and chimeras of Smad6 and Smad7 revealed that the MH2 domains were responsible for the inhibition of both TGF-β and BMP signaling by I-Smads, but the isolated MH2 domains of Smad6 and Smad7 were less potent than the full-length Smad7 in inhibiting TGF-β signaling. The N domains of I-Smads determined the subcellular localization of these molecules. Chimeras containing the N domain of Smad7 interacted with the TGF-β type I receptor (TβR-I) more efficiently, and were more potent in repressing TGF-β signaling, than those containing the N domain of Smad6. The isolated N domain of Smad7 physically interacted with the MH2 domain of Smad7, and enhanced the inhibitory activity of the latter through facilitating interaction with TGF-β receptors. The N domain of Smad7 thus plays an important role in the specific inhibition of TGF-β signaling.
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影响因子：
64.8
作者：
Imamura, T;Takase, M;Miyazono, K
通讯作者：
Miyazono, K
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11.4
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4.8
作者：
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10.5
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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