The MAD-related protein Smad7 associates with the TGF beta receptor and functions as an antagonist of TGF beta signaling
The MAD-related protein Smad7 associates with the TGF beta receptor and functions as an antagonist of TGF beta signaling
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DOI：
10.1016/s0092-8674(00)80303-7
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发表时间：
1997-06-27
期刊：
影响因子：
64.5
通讯作者：
Falb, D
中科院分区：
文献类型：
--
作者：
Hayashi, H;Abdollah, S;Falb, D
当I型受体磷酸化C末端丝氨酸残基上的MAD相关蛋白Smad 2时，TGF β信号传导启动。这导致Smad 2与Smad 4结合，易位到细胞核，并调节转录反应。在这里，我们证明Smad 7是TGF β信号传导的抑制剂。Smad 7阻止Smad 2/Smad 4复合物的TGF β依赖性形成并抑制Smad 2的核积聚。Smad 7与活化的TGF β I型受体稳定相互作用，从而阻断Smad 2的缔合、磷酸化和活化。此外，干扰受体结合的Smad 7突变会破坏其抑制活性。因此，这些研究定义了MAD相关蛋白作为TGF β家族受体I型激酶结构域的细胞内拮抗剂的新功能。
TGF beta signaling is initiated when the type I receptor phosphorylates the MAD-related protein, Smad2, on C-terminal serine residues. This leads to Smad2 association with Smad4, translocation to the nucleus, and regulation of transcriptional responses. Here we demonstrate that Smad7 is an inhibitor of TGF beta signaling. Smad7 prevents TGF beta-dependent formation of Smad2/Smad4 complexes and inhibits the nuclear accumulation of Smad2. Smad7 interacts stably with the activated TGF beta type I receptor, thereby blocking the association, phosphorylation, and activation of Smad2. Furthermore, mutations in Smad7 that interfere with receptor binding disrupt its inhibitory activity. These studies thus define a novel function for MAD-related proteins as intracellular antagonists of the type I kinase domain of TGF beta family receptors.