Phosphorylation regulation of the interaction between Smad7 and activin type I receptor.
Phosphorylation regulation of the interaction between Smad7 and activin type I receptor.
复制标题
Smad7 和激活素 I 型受体之间相互作用的磷酸化调节。
DOI：
10.1016/s0014-5793(02)02718-7
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发表时间：
2002
期刊：
影响因子：
3.5
通讯作者：
Chen,Yan
中科院分区：
文献类型：
--
作者：
Liu,Xubao;Nagarajan,RamanP;Vale,Wylie;Chen,Yan
激活素是转化生长因子-β超家族的成员之一，其信号转导是通过配体与两种不同的膜受体（II型和I型）结合，然后激活Smad2或Smad3而启动的。我们在这里报道激活素诱导的信号被另一个Smad分子Smad7负调控。当Smad7在中国仓鼠卵巢细胞中表达时，Smad7抑制激活素处理或组成活性激活素I型受体（ALK-4）诱导的转录反应。此外，Smad7还抑制了组成型活性ALK-4刺激的小鼠fast -2介导的Xenopus mix2启动子的转激活。Smad7能够直接与ALK-4结合，这种结合依赖于激活素II型受体在其GS结构域磷酸化I型受体。激酶缺陷激活素II型受体的表达降低了Smad7与ALK-4的关联。相应地，Smad7与突变体ALK-4结合不良，在其GS结构域的四个假定的磷酸化位点上有丝氨酸到丙氨酸的取代。这些研究不仅说明了Smad7对激活素信号的反调控作用，还提示了激活素I型受体磷酸化参与了Smad7的抑制作用。
Signal transduction of activin, one of the members in the transforming growth factor-β superfamily, is initiated by ligand binding with two distinct membrane receptors (type II and type I) followed by activation of Smad2 or Smad3. We report here that activin-induced signaling is negatively regulated by another Smad molecule, Smad7. When expressed in Chinese hamster ovary cells, Smad7 inhibited the transcriptional response induced by either activin treatment or a constitutively active activin type I receptor (ALK-4). In addition, Smad7 also inhibited mouse FAST-2-mediated transactivation of the Xenopus Mix.2 promoter stimulated by the constitutively active ALK-4. Smad7 was able to directly associate with ALK-4 and this association was dependent on the phosphorylation of the type I receptor in its GS domain by activin type II receptors. Expression of kinase defective activin type II receptors decreased the association of Smad7 with ALK-4. Correspondingly, Smad7 bound poorly to a mutant ALK-4 bearing serine to alanine substitutions in four putative phosphorylation sites in its GS domain. These studies not only illustrated the counter regulatory function of Smad7 on activin signaling, but also indicated the involvement of phosphorylation at activin type I receptor in the inhibitory action of Smad7.