Regulation of the Hippo–YAP pathway by protease-activated receptors (PARs)
- 1Department of Pharmacology, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA;
- 2Institute of Biochemical Sciences, Fudan University, Shanghai 200032, China
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 G12/13 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.
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Footnotes
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↵3 Corresponding author
E-mail kuguan{at}ucsd.edu
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.197582.112.
- Received May 30, 2012.
- Accepted August 6, 2012.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press
Freely available online through the Genes & Development Open Access option.