• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >The tyrosine Y250(2.39) in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled
【24h】

The tyrosine Y250(2.39) in Frizzled 4 defines a conserved motif important for structural integrity of the receptor and recruitment of Disheveled

机译：Flizzled 4中的酪氨酸Y250（2.39）定义了对受体的结构完整性的保守基板，并招募蓬乱

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

Frizzleds (FZDs) are unconventional G protein-coupled receptors, which activate diverse intracellular signaling pathways via the phosphoprotein Disheveled (DVL) and heterotrimeric G proteins. The Interaction interplay of FZDs with DVL and G proteins is complex, involves different regions of FZD and the potential dynamics are poorly understood. In the present study, we aimed to characterize the function of a highly conserved tyrosine (Y250(2.39)) in the intracellular loop 1 (ILl) of human FZD(4). We have found Y250(2.39) to be crucial for DVL2 interaction and DVL2 translocation to the plasma membrane. Mutant FZD4-Y250(2.39)F, impaired in DVL2 binding, was defective in both beta-catenin-dependent and beta-catenin-independent WNT signaling induced in Xenopus laevis embryos. The same mutant maintained interaction with the heterotrimeric G proteins Gan and G alpha(13) and was able to mediate WNT-induced G protein dissociation and G protein-dependent YAP/TAZ signaling. We conclude from modeling and dynamics simulation efforts that Y250(2.39) is important for the structural integrity of the FZD-DVL, but not for the FZD-G protein interface and hypothesize that the interaction network of Y250(2.39) and H348(4.46) plays a role in specifying downstream signaling pathways induced by the receptor.
机译：Frizzled（FZDs）是一种非传统的G蛋白偶联受体，通过磷酸化蛋白Disheveled（DVL）和异源三聚体G蛋白激活多种细胞内信号通路。FZD与DVL和G蛋白的相互作用是复杂的，涉及FZD的不同区域，潜在的动力学机制尚不清楚。在本研究中，我们旨在描述人类FZD（4）细胞内环1（ILl）中高度保守的酪氨酸（Y250（2.39））的功能。我们发现Y250（2.39）对DVL2相互作用和DVL2向质膜的易位至关重要。突变体FZD4-Y250（2.39）F在爪蟾胚胎中诱导的β-连环蛋白依赖性和β-连环蛋白非依赖性WNT信号中均存在缺陷，DVL2结合受损。同一突变体与异源三聚体G蛋白Gan和Gα（13）保持相互作用，并且能够介导WNT诱导的G蛋白解离和G蛋白依赖的YAP/TAZ信号。我们通过建模和动力学模拟得出结论，Y250（2.39）对FZD-DVL的结构完整性很重要，但对FZD-G蛋白质界面不重要，并假设Y250（2.39）和H348（4.46）的相互作用网络在指定受体诱导的下游信号通路中起作用。

著录项

  • 来源
    《Cellular Signalling》 |2017年第2017期|共12页
  • 作者

    Strakova Katerina; Matricon Pierre; Yokota Chika; Arthofer Elisa; Bernatik Ondrej; Rodriguez David; Arenas Ernest; Carlsson Jens; Bryja Viterslav; Schulte Gunnar;

  • 作者单位

    Masaryk Univ Fac Sci Inst Expt Biol Lab WNT Signaling Kotiarska 2 Brno 61137 Czech Republic;

    Uppsala Univ Sci Life Lab Dept Cell &

    Mol Biol SE-75124 Uppsala Sweden;

    Karolinska Inst Dept Med Biochem &

    Biophys Lab Mol Neurobiol Scheelevag 2 S-17177 Stockholm Sweden;

    Eunice Kennedy Shriver Natl Inst Child Hlth &

    Hum Sect Mol Signal Transduct NIH 35A Convent Dr MSC 3752 Bethesda MD 20892 USA;

    Masaryk Univ Fac Sci Inst Expt Biol Lab WNT Signaling Kotiarska 2 Brno 61137 Czech Republic;

    Stockholm Univ Dept Biochem &

    Biophys SE-10691 Stockholm Sweden;

    Karolinska Inst Dept Med Biochem &

    Biophys Lab Mol Neurobiol Scheelevag 2 S-17177 Stockholm Sweden;

    Uppsala Univ Sci Life Lab Dept Cell &

    Mol Biol SE-75124 Uppsala Sweden;

    Masaryk Univ Fac Sci Inst Expt Biol Lab WNT Signaling Kotiarska 2 Brno 61137 Czech Republic;

    Masaryk Univ Fac Sci Inst Expt Biol Lab WNT Signaling Kotiarska 2 Brno 61137 Czech Republic;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    Disheveled; DVL2; Frizzled; FZD(4); GNA12; GNA13;

    机译：蓬乱;DVL2;FRIZEDLED;FZD（4）;GNA12;GNA13;

相似文献

  • 外文文献
  • 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