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整合依赖β-连环蛋白的 Wnt 通路与整联蛋白信号通过衔接分子 Grb2。

Integration of the beta-catenin-dependent Wnt pathway with integrin signaling through the adaptor molecule Grb2.

机构信息

Department of Molecular Biology and Biochemistry, UCI Institute for Immunology, University of California Irvine, Irvine, California, USA.

出版信息

PLoS One. 2009 Nov 16;4(11):e7841. doi: 10.1371/journal.pone.0007841.

DOI:10.1371/journal.pone.0007841
PMID:19924227
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2773007/
Abstract

BACKGROUND

THE COMPLEXITY OF WNT SIGNALING LIKELY STEMS FROM TWO SOURCES: multiple pathways emanating from frizzled receptors in response to wnt binding, and modulation of those pathways and target gene responsiveness by context-dependent signals downstream of growth factor and matrix receptors. Both rac1 and c-jun have recently been implicated in wnt signaling, however their upstream activators have not been identified.

METHODOLOGY/PRINCIPAL FINDINGS: Here we identify the adapter protein Grb2, which is itself an integrator of multiple signaling pathways, as a modifier of beta-catenin-dependent wnt signaling. Grb2 synergizes with wnt3A, constitutively active (CA) LRP6, Dvl2 or CA-beta-catenin to drive a LEF/TCF-responsive reporter, and dominant negative (DN) Grb2 or siRNA to Grb2 block wnt3A-mediated reporter activity. MMP9 is a target of beta-catenin-dependent wnt signaling, and an MMP9 promoter reporter is also responsive to signals downstream of Grb2. Both a jnk inhibitor and DN-c-jun block transcriptional activation downstream of Dvl2 and Grb2, as does DN-rac1. Integrin ligation by collagen also synergizes with wnt signaling as does overexpression of Focal Adhesion Kinase (FAK), and this is blocked by DN-Grb2.

CONCLUSIONS/SIGNIFICANCE: These data suggest that integrin ligation and FAK activation synergize with wnt signaling through a Grb2-rac-jnk-c-jun pathway, providing a context-dependent mechanism for modulation of wnt signaling.

摘要

背景

WNT 信号的复杂性可能源于两个来源：从卷曲受体发出的多条途径，以响应 WNT 结合，以及通过生长因子和基质受体下游的上下文相关信号来调节这些途径和靶基因反应性。Rac1 和 c-jun 最近都被牵连到 WNT 信号中，但其上游激活剂尚未确定。

方法/主要发现：在这里，我们确定了衔接蛋白 Grb2 作为一种修饰物，它本身就是多种信号通路的整合者，作为β-catenin 依赖性 WNT 信号的修饰物。Grb2 与 Wnt3A、组成型激活（CA）LRP6、Dvl2 或 CA-β-catenin 协同作用，驱动 LEF/TCF 反应性报告器，而显性负（DN）Grb2 或 Grb2 的 siRNA 阻断 Wnt3A 介导的报告器活性。MMP9 是β-catenin 依赖性 WNT 信号的靶标，MMP9 启动子报告器也对 Grb2 下游的信号有反应。JNK 抑制剂和 DN-c-jun 阻断 Dvl2 和 Grb2 下游的转录激活，DN-rac1 也是如此。胶原整合素的黏附也与 WNT 信号协同作用，FAK 的过表达也是如此，而这被 DN-Grb2 阻断。

结论/意义：这些数据表明，整合素黏附和 FAK 激活通过 Grb2-rac-jnk-c-jun 途径与 WNT 信号协同作用，为 WNT 信号的调节提供了一种上下文相关的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/a03c63f92ed7/pone.0007841.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/56d7d0d423c0/pone.0007841.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/bc5d728b429d/pone.0007841.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/271edd5da512/pone.0007841.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/002e22d1b2b8/pone.0007841.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/c7564a0b77d4/pone.0007841.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/25abca57c018/pone.0007841.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/2f543e061389/pone.0007841.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/a03c63f92ed7/pone.0007841.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/56d7d0d423c0/pone.0007841.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/bc5d728b429d/pone.0007841.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/271edd5da512/pone.0007841.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/002e22d1b2b8/pone.0007841.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/c7564a0b77d4/pone.0007841.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/25abca57c018/pone.0007841.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/2f543e061389/pone.0007841.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0688/2773007/a03c63f92ed7/pone.0007841.g008.jpg

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3
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5
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