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Genes Dev. 2012 Oct 1;26(19):2138-43. doi: 10.1101/gad.197582.112. Epub 2012 Sep 12.

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

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  • 1Department of Pharmacology, Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA.

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.

PMID:
22972936
PMCID:
PMC3465735
DOI:
10.1101/gad.197582.112
[PubMed - indexed for MEDLINE]
Free PMC Article
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