...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus
【24h】

Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus

机译：组成性抑制蛋白介导的与人为肾病性尿崩症相关的人血管加压素受体突变体的脱敏

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Agonist-dependent desensitization and internalization of G protein- coupled recePtors (GPCR) are mediated by the binding of arrestins to phosphorylated receptors. The affinity of arrestins for the phosphor- ylated GPCR regulates the ability of the intemalized receptor to be dephosphorylated and recycled back to the plasma membrane. In this study, we show that the naturally occurring loss of function vasopressin receptor mutation R137H, which is associated with fa- milial nephrogenic diabetes insipidus, induces constitutive arrestin- mediated desensitization. In contrast to the wildnype vasopressin receptor, the nonsignaling R137H recePtor is phosphorylated and sequestered in arrestin-associated intracellular vesicles even in the absence of agonist. Eliminating molecular determinants on the re- ceptor that promote high affinity arrestin--receptor interaction rees- tablishes plasma membrane localization and the ability of the mu- tated receptors to signal. These findings suggest that unregulated desensitization can contribute to the etiology of a GPCR-based dis- ease, implying that pharmacological targoting of GPCR desensitiza- tion may be therapeutically beneficial.
机译：G蛋白偶联受体（GPCR）的激动剂依赖性脱敏和内在化是通过抑制蛋白与磷酸化受体的结合来介导的。抑制蛋白对磷酸化GPCR的亲和力调节了内化受体被去磷酸化并循环回到质膜的能力。在这项研究中，我们表明，天然存在的功能性加压素受体突变R137H的丧失与军方肾原性尿崩症有关，它诱导了本构性的抑制素介导的脱敏。与野生型加压素受体相反，即使在没有激动剂的情况下，无信号的R137H受体也被磷酸化并螯合在与抑制素相关的细胞内囊泡中。消除受体上促进高亲和力的抑制蛋白-受体相互作用的分子决定因素，可以使质膜定位和突变受体发出信号的能力得以增强。这些发现表明，失控的脱敏可以导致基于GPCR的疾病的病因，这意味着GPCR脱敏的药理学反应可能对治疗有益。

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