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机械转导、Hippo、Wnt 和 TGFβ 有什么共同之处?YAP 和 TAZ 作为眼部健康和疾病中的关键协调分子。

What do mechanotransduction, Hippo, Wnt, and TGFβ have in common? YAP and TAZ as key orchestrating molecules in ocular health and disease.

机构信息

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, 1 Shields Ave., Davis, CA 95616, USA.

出版信息

Exp Eye Res. 2013 Oct;115:1-12. doi: 10.1016/j.exer.2013.06.012. Epub 2013 Jun 20.

Abstract

Cells in vivo are exposed to a complex signaling environment. Biochemical signaling modalities, such as secreted proteins, specific extracellular matrix domains and ion fluxes certainly compose an important set of regulatory signals to cells. However, these signals are not exerted in isolation, but rather in concert with biophysical cues of the surrounding tissue, such as stiffness and topography. In this review, we attempt to highlight the biophysical attributes of ocular tissues and their influence on cellular behavior. Additionally, we introduce the proteins YAP and TAZ as targets of biophysical and biochemical signaling and important agonists and antagonists of numerous signaling pathways, including TGFβ and Wnt. We frame the discussion around this extensive signaling crosstalk, which allows YAP and TAZ to act as orchestrating molecules, capable of integrating biophysical and biochemical cues into a broad cellular response. Finally, while we draw on research from various fields to provide a full picture of YAP and TAZ, we attempt to highlight the intersections with vision science and the exciting work that has already been performed.

摘要

细胞在体内处于复杂的信号环境中。生化信号方式,如分泌蛋白、特定的细胞外基质结构域和离子流,当然构成了细胞的一组重要调节信号。然而,这些信号并非孤立作用,而是与周围组织的生物物理线索协同作用,如硬度和形貌。在这篇综述中,我们试图强调眼部组织的生物物理特性及其对细胞行为的影响。此外,我们介绍了 YAP 和 TAZ 这两种蛋白,它们是生物物理和生化信号的靶点,也是 TGFβ 和 Wnt 等众多信号通路的重要激动剂和拮抗剂。我们围绕这一广泛的信号串扰展开讨论,该串扰使 YAP 和 TAZ 能够作为协调分子,将生物物理和生化线索整合到广泛的细胞反应中。最后,虽然我们借鉴了来自不同领域的研究来全面了解 YAP 和 TAZ,但我们试图突出与视觉科学的交叉点以及已经完成的令人兴奋的工作。

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本文引用的文献

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The Hippo pathway and human cancer.Hippo 通路与人类癌症。
Nat Rev Cancer. 2013 Apr;13(4):246-57. doi: 10.1038/nrc3458. Epub 2013 Mar 7.
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Mask proteins are cofactors of Yorkie/YAP in the Hippo pathway.膜蛋白是 Hippo 通路中 Yorkie/YAP 的辅助因子。
Curr Biol. 2013 Feb 4;23(3):223-8. doi: 10.1016/j.cub.2012.11.061. Epub 2013 Jan 17.
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Role of TAZ as mediator of Wnt signaling.TAZ 在 Wnt 信号转导中的作用。
Cell. 2012 Dec 21;151(7):1443-56. doi: 10.1016/j.cell.2012.11.027. Epub 2012 Dec 13.
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