APPL1是一种多功能的内体信号衔接蛋白。
APPL1 is a multifunctional endosomal signaling adaptor protein.
作者信息
Diggins Nicole L, Webb Donna J
机构信息
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, U.S.A.
Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN 37235, U.S.A.
出版信息
Biochem Soc Trans. 2017 Jun 15;45(3):771-779. doi: 10.1042/BST20160191.
Abstract
Endosomal adaptor proteins are important regulators of signaling pathways underlying many biological processes. These adaptors can integrate signals from multiple pathways via localization to specific endosomal compartments, as well as through multiple protein-protein interactions. One such adaptor protein that has been implicated in regulating signaling pathways is the daptor protein containing a leckstrin homology (PH) domain, hosphotyrosine-binding (PTB) domain, and eucine zipper motif 1 (APPL1). APPL1 localizes to a subset of Rab5-positive endosomes through its Bin-Amphiphysin-Rvs and PH domains, and it coordinates signaling pathways through its interaction with many signaling receptors and proteins through its PTB domain. This review discusses our current understanding of the role of APPL1 in signaling and trafficking, as well as highlights recent work into the function of APPL1 in cell migration and adhesion.
摘要
内体衔接蛋白是许多生物学过程所依赖的信号通路的重要调节因子。这些衔接蛋白可通过定位于特定的内体区室以及通过多种蛋白质-蛋白质相互作用来整合来自多个通路的信号。一种与调节信号通路有关的衔接蛋白是含有leckstrin同源（PH）结构域、磷酸酪氨酸结合（PTB）结构域和亮氨酸拉链基序1（APPL1）的衔接蛋白。APPL1通过其Bin- Amphiphysin-Rvs和PH结构域定位于Rab5阳性内体的一个亚群，并通过其PTB结构域与许多信号受体和蛋白质的相互作用来协调信号通路。本综述讨论了我们目前对APPL1在信号传导和运输中的作用的理解，并着重介绍了最近关于APPL1在细胞迁移和黏附中功能的研究工作。
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本文引用的文献
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Oncotarget. 2016 Jan 5;7(1):279-92. doi: 10.18632/oncotarget.6346.
2
APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments.APPL内体不是必需的内吞中间体，而是作为稳定的货物分拣区室发挥作用。
J Cell Biol. 2015 Oct 12;211(1):123-44. doi: 10.1083/jcb.201311117.
3
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FEBS Lett. 2015 Feb 13;589(4):532-9. doi: 10.1016/j.febslet.2015.01.022. Epub 2015 Jan 23.
4
ESCRT-0 marks an APPL1-independent transit route for EGFR between the cell surface and the EEA1-positive early endosome.ESCRT-0标志着表皮生长因子受体（EGFR）在细胞表面和早期核内体抗原1（EEA1）阳性早期内体之间的一条不依赖APPL1的转运途径。
J Cell Sci. 2015 Feb 15;128(4):755-67. doi: 10.1242/jcs.161786. Epub 2015 Jan 14.
5
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J Biol Chem. 2014 Oct 31;289(44):30237-30248. doi: 10.1074/jbc.M114.596155. Epub 2014 Sep 15.
6
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7
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J Cell Sci. 2014 Jun 1;127(Pt 11):2401-6. doi: 10.1242/jcs.141689. Epub 2014 Mar 21.
8
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9
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J Cell Sci. 2013 Sep 1;126(Pt 17):3835-47. doi: 10.1242/jcs.119727. Epub 2013 Jun 26.
10
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