...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Two C-terminal amino acids, Ser(334) and Ser(335), are required for homologous desensitization and agonist-induced phosphorylation of opioid receptor-like 1 receptors
【24h】

Two C-terminal amino acids, Ser(334) and Ser(335), are required for homologous desensitization and agonist-induced phosphorylation of opioid receptor-like 1 receptors

机译：同源脱敏和激动剂诱导的阿片受体样1受体磷酸化需要两个C末端氨基酸Ser（334）和Ser（335）

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

Various cellular signaling pathways induced by nociceptin activation of ORL1 (opioid receptor-like I receptor) develop homologous desensitization. Multiple lines of evidence suggest that agonist-induced phosphorylation of serine (Ser)/threonine (Thr) residues at intracellular carboxyl tail leads to homologous desensitization of G protein-coupled receptors. In the present study, we investigated the functional role played by C-terminal Ser/Thr residues in agonist-induced desensitization and phosphorylation of ORL1. In HEK 293 cells expressing wild-type ORL1 and ORL1(C Delta 21), which lacks C-terminal 21 amino acids, nociceptin inhibition of adenylate cyclase activity exhibited homologous desensitization after 1 h pretreatment of nociceptin. In contrast, ORL1(C Delta 34), which differs with ORL1(C Delta 21) by lacking C-terminal Ser(334), Ser(353) and Ser(343) residues, failed to develop agonist-induced desensitization. Point mutant (S343A) ORL1 underwent homologous desensitization after nociceptin pretreatment. Substituting Ser(334) or Ser(335) with alanine greatly impaired nociceptin-induced ORL1 desensitization. In HEK 293 cells expressing double mutant (S334A/S335A) ORL1, nociceptin pretreatment failed to significantly affect the efficacy and potency by which nociceptin inhibits forskolin-stimulated cAMP formation. Mutation of Ser 334 and Ser 335 also greatly reduced nociceptin-induced ORL1 phosphorylation. These results suggest that two C-terminal serine residues, Ser 334 and Ser 335, are required for homologous desensitization and agonist-induced phosphorylation of ORL1. (c) 2005 Published by Elsevier Inc.
机译：由伤害感受器激活ORL1（类阿片受体样I受体）诱导的各种细胞信号通路均发生同源脱敏。多条证据表明，激动剂诱导的细胞内羧基尾丝氨酸（Ser）/苏氨酸（Thr）残基的磷酸化导致G蛋白偶联受体的同源脱敏。在本研究中，我们研究了C末端Ser / Thr残基在激动剂诱导的ORL1脱敏和磷酸化中发挥的功能。在表达野生型ORL1和ORL1（C Delta 21）（缺乏C端21个氨基酸）的HEK 293细胞中，伤害感受器预处理1小时后，伤害感受器抑制腺苷酸环化酶活性表现出同源的脱敏作用。相反，ORL1（C Delta 34）与ORL1（C Delta 21）的不同之处在于缺少C端Ser（334），Ser（353）和Ser（343）残基，未能引起激动剂引起的脱敏。点突变（S343A）ORL1在伤害感受素预处理后经历了同源脱敏。用丙氨酸替代Ser（334）或Ser（335）大大削弱了伤害感受素诱导的ORL1脱敏。在表达双突变体（S334A / S335A）ORL1的HEK 293细胞中，伤害感受素的预处理未能显着影响伤害感受素抑制毛喉素刺激的cAMP形成的功效。 Ser 334和Ser 335的突变也大大减少了伤害感受素诱导的ORL1磷酸化。这些结果表明，ORL1的同源脱敏和激动剂诱导的磷酸化需要两个C端丝氨酸残基Ser 334和Ser 335。 （c）2005年由Elsevier Inc.发布。

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