蛋白酶激活受体（PARs）对 Hippo-YAP 通路的调控。
Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs).
机构信息
Department of Pharmacology, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA.
出版信息
Genes Dev. 2012 Oct 1;26(19):2138-43. doi: 10.1101/gad.197582.112. Epub 2012 Sep 12.
Abstract
The Hippo signaling pathway plays a crucial role in tissue growth and tumorigenesis. Core components of the Hippo pathway include the MST1/2 and Lats1/2 kinases. Acting downstream from the Hippo pathway are the YAP/TAZ transcription coactivators, which are inhibited through phosphorylation by Lats. However, upstream signals that regulate the Hippo pathway have not been well delineated. Here we report that stimulation of protease-activated receptors (PARs) activates YAP/TAZ by decreasing phosphorylation and increasing nuclear localization. PAR1 acts through G(12/13) and Rho GTPase to inhibit the Lats1/2 kinase. Our observations establish thrombin as a physiological signal for the Hippo pathway and implicate Hippo-YAP as a key downstream signaling branch of PAR activation.
摘要
Hippo 信号通路在组织生长和肿瘤发生中起着至关重要的作用。Hippo 通路的核心组成部分包括 MST1/2 和 Lats1/2 激酶。Hippo 通路的下游是 YAP/TAZ 转录共激活因子，它们通过 Lats 的磷酸化而被抑制。然而，调节 Hippo 通路的上游信号尚未得到很好的描述。在这里，我们报告说，蛋白酶激活受体（PARs）的刺激通过减少磷酸化和增加核定位来激活 YAP/TAZ。PAR1 通过 G(12/13)和 Rho GTPase 抑制 Lats1/2 激酶。我们的观察结果确立了凝血酶作为 Hippo 通路的生理信号，并暗示 Hippo-YAP 是 PAR 激活的关键下游信号分支。
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