The RGS-RhoGEFs control the amplitude of YAP1 activation by serum

Abstract Actin-dependent mechanisms drive the nuclear translocation of Yap1 to enable its co-activation of transcription factors that induce pro-growth and survival programs. While Rho GTPases are necessary for the nuclear import of YAP1, the relevant Guanine Exchange Factors (GEFs) and GTPase Activ...

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Autores principales:	Brandon S. Lane, Brigitte Heller, Morley D. Hollenberg, Clark D. Wells
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/266df4df734b483da8761711da4de944
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spelling	oai:doaj.org-article:266df4df734b483da8761711da4de9442021-12-02T13:57:49ZThe RGS-RhoGEFs control the amplitude of YAP1 activation by serum10.1038/s41598-021-82027-42045-2322https://doaj.org/article/266df4df734b483da8761711da4de9442021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82027-4https://doaj.org/toc/2045-2322Abstract Actin-dependent mechanisms drive the nuclear translocation of Yap1 to enable its co-activation of transcription factors that induce pro-growth and survival programs. While Rho GTPases are necessary for the nuclear import of YAP1, the relevant Guanine Exchange Factors (GEFs) and GTPase Activating Proteins (GAPs) that connect this process to upstream signaling are not well defined. To this end, we measured the impact of expressing sixty-seven RhoGEFs and RhoGAPs on the YAP1 dependent activity of a TEAD element transcriptional reporter. Robust effects by all three members of the regulator of G-protein signaling (RGS) domain containing RhoGEFs (ArhGEF1, ArhGEF11 and ArhGEF12) prompted studies relating their known roles in serum signaling onto the regulation of Yap1. Under all conditions examined, ArhGEF12 preferentially mediated the activation of YAP1/TEAD by serum versus ArhGEF1 or ArhGEF11. Conversely, ArhGEF1 in multiple contexts inhibited both basal and serum elevated YAP1 activity through its GAP activity for Gα13. The sensitivity of such inhibition to cellular density and to low states of serum signaling supports that ArhGEF1 is a context dependent regulator of YAP1. Taken together, the relative activities of the RGS-RhoGEFs were found to dictate the degree to which serum signaling promotes YAP1 activity.Brandon S. LaneBrigitte HellerMorley D. HollenbergClark D. WellsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brandon S. Lane Brigitte Heller Morley D. Hollenberg Clark D. Wells The RGS-RhoGEFs control the amplitude of YAP1 activation by serum
description	Abstract Actin-dependent mechanisms drive the nuclear translocation of Yap1 to enable its co-activation of transcription factors that induce pro-growth and survival programs. While Rho GTPases are necessary for the nuclear import of YAP1, the relevant Guanine Exchange Factors (GEFs) and GTPase Activating Proteins (GAPs) that connect this process to upstream signaling are not well defined. To this end, we measured the impact of expressing sixty-seven RhoGEFs and RhoGAPs on the YAP1 dependent activity of a TEAD element transcriptional reporter. Robust effects by all three members of the regulator of G-protein signaling (RGS) domain containing RhoGEFs (ArhGEF1, ArhGEF11 and ArhGEF12) prompted studies relating their known roles in serum signaling onto the regulation of Yap1. Under all conditions examined, ArhGEF12 preferentially mediated the activation of YAP1/TEAD by serum versus ArhGEF1 or ArhGEF11. Conversely, ArhGEF1 in multiple contexts inhibited both basal and serum elevated YAP1 activity through its GAP activity for Gα13. The sensitivity of such inhibition to cellular density and to low states of serum signaling supports that ArhGEF1 is a context dependent regulator of YAP1. Taken together, the relative activities of the RGS-RhoGEFs were found to dictate the degree to which serum signaling promotes YAP1 activity.
format	article
author	Brandon S. Lane Brigitte Heller Morley D. Hollenberg Clark D. Wells
author_facet	Brandon S. Lane Brigitte Heller Morley D. Hollenberg Clark D. Wells
author_sort	Brandon S. Lane
title	The RGS-RhoGEFs control the amplitude of YAP1 activation by serum
title_short	The RGS-RhoGEFs control the amplitude of YAP1 activation by serum
title_full	The RGS-RhoGEFs control the amplitude of YAP1 activation by serum
title_fullStr	The RGS-RhoGEFs control the amplitude of YAP1 activation by serum
title_full_unstemmed	The RGS-RhoGEFs control the amplitude of YAP1 activation by serum
title_sort	rgs-rhogefs control the amplitude of yap1 activation by serum
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/266df4df734b483da8761711da4de944
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The RGS-RhoGEFs control the amplitude of YAP1 activation by serum

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