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Regulation of the Hippo-YAP pathway by protease-activated receptors (PARs).

Research paper by Jung-Soon JS Mo, Fa-Xing FX Yu, Rui R Gong, Joan Heller JH Brown, Kun-Liang KL Guan

Indexed on: 14 Sep '12Published on: 14 Sep '12Published in: Genes & development



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.