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牵拉与推动:黏着斑蛋白激活整合素信号通路。

Pull and push: talin activation for integrin signaling.

机构信息

College of Life Sciences, Peking University, Beijing 100871, China [2] Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

出版信息

Cell Res. 2012 Nov;22(11):1512-4. doi: 10.1038/cr.2012.103. Epub 2012 Jul 10.

DOI:10.1038/cr.2012.103
PMID:22777425
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3494393/
Abstract

The inside-out signaling of integrins regulates the ligand-binding affinity of the cell surface receptors in response to changes in the environment for cell survival. The specific binding to the cytoplasmic tail of integrin's β subunit by the intracellular protein talin is the key step of inside-out signaling. A "pull-push" mechanism has been proposed to explain how the PIP2-enriched membrane disrupts the dual auto-inhibition of the N-terminal talin-FERM domain by the C-terminal talin-rod domain such that activated talin-FERM can reach the β-tail for integrin activation.

摘要

整联蛋白的内信号转导通过调节细胞表面受体与配体的结合亲和力,从而响应细胞生存环境的变化。细胞内蛋白 talin 通过特异性结合整联蛋白β亚基的胞质尾,是内信号转导的关键步骤。一种“拉-推”机制被提出用来解释富含 PIP2 的膜如何破坏 N 端 talin-FERM 域对 C 端 talin-rod 域的双重自身抑制,从而使激活的 talin-FERM 能够到达β-尾以激活整联蛋白。

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Pull and push: talin activation for integrin signaling.牵拉与推动:黏着斑蛋白激活整合素信号通路。
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2
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本文引用的文献

1
A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion.一种新型的依赖于细胞膜的粘着斑连接蛋白FERM 结构域的开/关开关机制。
Cell Res. 2012 Nov;22(11):1533-45. doi: 10.1038/cr.2012.97. Epub 2012 Jun 19.
2
Affinity of talin-1 for the β3-integrin cytosolic domain is modulated by its phospholipid bilayer environment.桩蛋白 1 与β3 整合素胞质结构域的亲和力受其磷脂双分子层环境调节。
Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):793-8. doi: 10.1073/pnas.1117220108. Epub 2011 Dec 30.
3
The tail of integrin activation.整合素激活的尾部。
Trends Biochem Sci. 2011 Apr;36(4):191-8. doi: 10.1016/j.tibs.2010.11.002. Epub 2011 Jan 6.
4
The structure of an integrin/talin complex reveals the basis of inside-out signal transduction.整合素/踝蛋白复合物的结构揭示了由内向外信号转导的基础。
EMBO J. 2009 Nov 18;28(22):3623-32. doi: 10.1038/emboj.2009.287. Epub 2009 Oct 1.
5
The tail of integrins, talin, and kindlins.整合素、踝蛋白和纽带蛋白的尾部。
Science. 2009 May 15;324(5929):895-9. doi: 10.1126/science.1163865.
6
Biochemical and structural properties of the integrin-associated cytoskeletal protein talin.整合素相关细胞骨架蛋白踝蛋白的生化与结构特性
Annu Rev Biophys. 2009;38:235-54. doi: 10.1146/annurev.biophys.050708.133744.
7
Structural basis for the autoinhibition of talin in regulating integrin activation.踝蛋白在调节整合素激活过程中自我抑制的结构基础。
Mol Cell. 2008 Jul 11;31(1):124-33. doi: 10.1016/j.molcel.2008.06.011.
8
Structural basis of integrin regulation and signaling.整合素调节与信号传导的结构基础。
Annu Rev Immunol. 2007;25:619-47. doi: 10.1146/annurev.immunol.25.022106.141618.
9
The three-dimensional structure of integrins and their ligands, and conformational regulation of cell adhesion.整合素及其配体的三维结构以及细胞黏附的构象调节。
Adv Protein Chem. 2004;68:29-63. doi: 10.1016/S0065-3233(04)68002-8.
10
Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins.整合素中通过胞质结构域分离实现的双向跨膜信号传导。
Science. 2003 Sep 19;301(5640):1720-5. doi: 10.1126/science.1084174.