卷曲蛋白和 LRP5/6 受体在 Wnt/β-连环蛋白信号通路中的作用。
Frizzled and LRP5/6 receptors for Wnt/β-catenin signaling.
机构信息
The F. M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
出版信息
Cold Spring Harb Perspect Biol. 2012 Dec 1;4(12):a007880. doi: 10.1101/cshperspect.a007880.
Abstract
Frizzled and LRP5/6 are Wnt receptors that upon activation lead to stabilization of cytoplasmic β-catenin. In this study, we review the current knowledge of these two families of receptors, including their structures and interactions with Wnt proteins, and signaling mechanisms from receptor activation to the engagement of intracellular partners Dishevelled and Axin, and finally to the inhibition of β-catenin phosphorylation and ensuing β-catenin stabilization.
摘要
卷曲和 LRP5/6 是 Wnt 受体，它们在被激活后会导致细胞质 β-连环蛋白的稳定。在本研究中，我们回顾了这两个受体家族的现有知识，包括它们的结构以及与 Wnt 蛋白的相互作用，以及从受体激活到与细胞内伙伴 Dishevelled 和 Axin 的结合，最终到 β-连环蛋白磷酸化的抑制和随后的 β-连环蛋白稳定的信号机制。
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本文引用的文献
1
Mutations affecting the pattern of the larval cuticle inDrosophila melanogaster : I. Zygotic loci on the second chromosome.影响黑腹果蝇幼虫表皮模式的突变：I. 第二条染色体上的合子基因座。
Wilehm Roux Arch Dev Biol. 1984 Sep;193(5):267-282. doi: 10.1007/BF00848156.
2
The β-catenin destruction complex.β-连环蛋白降解复合物。
Cold Spring Harb Perspect Biol. 2013 Jan 1;5(1):a007898. doi: 10.1101/cshperspect.a007898.
3
β-catenin-dependent Wnt signaling in C. elegans: teaching an old dog a new trick.β-catenin 依赖性 Wnt 信号通路在秀丽隐杆线虫中的作用：教老狗新把戏。
Cold Spring Harb Perspect Biol. 2012 Aug 1;4(8):a007948. doi: 10.1101/cshperspect.a007948.
4
Structural basis of Wnt recognition by Frizzled.卷曲蛋白受体识别 Wnt 配体的结构基础。
Science. 2012 Jul 6;337(6090):59-64. doi: 10.1126/science.1222879. Epub 2012 May 31.
5
Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled.Wnt/β-catenin 信号通路需要 Dishevelled DEP 结构域和 C 端与 Frizzled 中不连续基序相互作用。
Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):E812-20. doi: 10.1073/pnas.1114802109. Epub 2012 Mar 12.
6
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EMBO Rep. 2012 Apr;13(4):347-54. doi: 10.1038/embor.2012.12.
7
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Sci Signal. 2012 Jan 10;5(206):ra3. doi: 10.1126/scisignal.2002274.
8
The extracellular loops of Smoothened play a regulatory role in control of Hedgehog pathway activation.Smoothened 的细胞外环在 Hedgehog 通路激活的调控中发挥作用。
Development. 2012 Feb;139(3):612-21. doi: 10.1242/dev.075614.
9
Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility.分泌的无翅型相互作用分子（Swim）通过维持无翅型的可溶性来促进长距离信号转导。
Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):370-7. doi: 10.1073/pnas.1119197109. Epub 2011 Dec 27.
10
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