Prospects & Overviews
G protein-coupled receptors engage the mammalian Hippo pathway through F-actin
F-Actin, assembled in response to Galpha12/13 induced RhoA-GTP, promotes dephosphorylation and activation of the YAP oncogene
Article first published online: 1 MAR 2013
Copyright © 2013 WILEY Periodicals, Inc.
Volume 35, Issue 5, pages 430–435, May 2013
How to Cite
Regué, L., Mou, F. and Avruch, J. (2013), G protein-coupled receptors engage the mammalian Hippo pathway through F-actin. Bioessays, 35: 430–435. doi: 10.1002/bies.201200163
- Issue published online: 12 APR 2013
- Article first published online: 1 MAR 2013
- G protein-coupled receptors;
The Hippo pathway, a cascade of protein kinases that inhibits the oncogenic transcriptional coactivators YAP and TAZ, was discovered in Drosophila as a major determinant of organ size in development. Known modes of regulation involve surface proteins that mediate cell-cell contact or determine epithelial cell polarity which, in a tissue-specific manner, use intracellular complexes containing FERM domain and actin-binding proteins to modulate the kinase activities or directly sequester YAP. Unexpectedly, recent work demonstrates that GPCRs, especially those signaling through Galpha12/13 such as the protease activated receptor PAR1, cause potent YAP dephosphorylation and activation. This response requires active RhoA GTPase and increased assembly of filamentous (F-)actin. Morever, cell architectures that promote F-actin assembly per se also activate YAP by kinase-dependent and independent mechanisms. These findings unveil the ability of GPCRs to activate the YAP oncogene through a newly recognized signaling function of the actin cytoskeleton, likely to be especially important for normal and cancerous stem cells.