• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Activation of signalling by the activin receptor complex.
【24h】

Activation of signalling by the activin receptor complex.

机译：激活素受体复合物激活信号传导。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Activin exerts its effects by simultaneously binding to two types of p rotein serine/threonine kinase receptors, each type existing in various isoforms. Using the ActR-IB and ActR-IIB receptor isoforms, we have investigated the mechanism of activin receptor activation. ActR-IIB are phosphoproteins with demonstrable affinity for each other. However, activin addition strongly promotes an interaction between these two proteins. Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own. In the resulting complex, ActR-IB becomes hyperphosphorylated, and this requires the kinase activity of ActR-IIB. Mutation of conserved serines and threonines in the GS domain, a region just upstream of the kinase domain in ActR-IB, abrogates both phosphorylation and signal propagation, suggesting that this domain contains phosphorylation sites required for signalling. ActR-IB activation can be mimicked by mutation of Thr-206 to aspartic acid, which yields a construct, ActR-IB(T206D), that signals in the absence of ligand. Furthermore, the signalling activity of this mutant construct is undisturbed by overexpression of a dominant negative kinase-defective ActR-IIB construct, indicating that ActR-IB(T206D) can signal independently of ActR-IIB. The evidence suggests that ActR-IIB acts as a primary activin receptor and ActR-IB acts as a downstream transducer of activin signals.
机译：激活素通过同时结合两种类型的蛋白白蛋白丝氨酸/苏氨酸激酶受体发挥作用，每种蛋白均以各种异构体形式存在。使用ActR-IB和ActR-IIB受体同工型，我们研究了激活素受体激活的机制。 ActR-IIB是彼此具有亲和力的磷蛋白。但是，激活素的添加强烈促进了这两种蛋白质之间的相互作用。激活素直接与ActR-IIB结合，并且该复合物与ActR-IB缔合，后者本身并不结合配体。在所得的复合物中，ActR-IB被过度磷酸化，这需要ActR-IIB的激酶活性。 GS域中保守丝氨酸和苏氨酸的突变（ActR-IB中激酶结构域的上游区域）消除了磷酸化和信号传播，这表明该结构域包含信号传导所需的磷酸化位点。可以通过将Thr-206突变为天冬氨酸来模拟ActR-IB的激活，这会产生一种在没有配体的情况下发出信号的构建体ActR-IB（T206D）。此外，该突变体构建体的信号传导活性不受显性负激酶缺陷的ActR-IIB构建体的过表达的干扰，表明ActR-IB（T206D）可以独立于ActR-IIB发出信号。证据表明，ActR-IIB充当主要的激活素受体，ActR-IB充当激活素信号的下游转导者。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号