Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.

The small GTPase RhoA is a central signaling enzyme that is involved in various cellular processes such as cytoskeletal dynamics, transcription, and cell cycle progression. Many signal transduction pathways activate RhoA-for instance, Gαq-coupled Histamine 1 Receptor signaling via Gαq-dependent acti...

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Autores principales:	Jason Z Zhang, Andy H Nguyen, Shigeki Miyamoto, Joan Heller Brown, Andrew D McCulloch, Jin Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2020
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0ebb54bacf2e4652ac3dc47d3752c53f
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spelling	oai:doaj.org-article:0ebb54bacf2e4652ac3dc47d3752c53f2021-12-02T19:54:27ZHistamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.1544-91731545-788510.1371/journal.pbio.3000866https://doaj.org/article/0ebb54bacf2e4652ac3dc47d3752c53f2020-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3000866https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The small GTPase RhoA is a central signaling enzyme that is involved in various cellular processes such as cytoskeletal dynamics, transcription, and cell cycle progression. Many signal transduction pathways activate RhoA-for instance, Gαq-coupled Histamine 1 Receptor signaling via Gαq-dependent activation of RhoGEFs such as p63. Although multiple upstream regulators of RhoA have been identified, the temporal regulation of RhoA and the coordination of different upstream components in its regulation have not been well characterized. In this study, live-cell measurement of RhoA activation revealed a biphasic increase of RhoA activity upon histamine stimulation. We showed that the first and second phase of RhoA activity are dependent on p63 and Ca2+/PKC, respectively, and further identified phosphorylation of serine 240 on p115 RhoGEF by PKC to be the mechanistic link between PKC and RhoA. Combined approaches of computational modeling and quantitative measurement revealed that the second phase of RhoA activation is insensitive to rapid turning off of the receptor and is required for maintaining RhoA-mediated transcription after the termination of the receptor signaling. Thus, two divergent pathways enable both rapid activation and persistent signaling in receptor-mediated RhoA signaling via intricate temporal regulation.Jason Z ZhangAndy H NguyenShigeki MiyamotoJoan Heller BrownAndrew D McCullochJin ZhangPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 18, Iss 9, p e3000866 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jason Z Zhang Andy H Nguyen Shigeki Miyamoto Joan Heller Brown Andrew D McCulloch Jin Zhang Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.
description	The small GTPase RhoA is a central signaling enzyme that is involved in various cellular processes such as cytoskeletal dynamics, transcription, and cell cycle progression. Many signal transduction pathways activate RhoA-for instance, Gαq-coupled Histamine 1 Receptor signaling via Gαq-dependent activation of RhoGEFs such as p63. Although multiple upstream regulators of RhoA have been identified, the temporal regulation of RhoA and the coordination of different upstream components in its regulation have not been well characterized. In this study, live-cell measurement of RhoA activation revealed a biphasic increase of RhoA activity upon histamine stimulation. We showed that the first and second phase of RhoA activity are dependent on p63 and Ca2+/PKC, respectively, and further identified phosphorylation of serine 240 on p115 RhoGEF by PKC to be the mechanistic link between PKC and RhoA. Combined approaches of computational modeling and quantitative measurement revealed that the second phase of RhoA activation is insensitive to rapid turning off of the receptor and is required for maintaining RhoA-mediated transcription after the termination of the receptor signaling. Thus, two divergent pathways enable both rapid activation and persistent signaling in receptor-mediated RhoA signaling via intricate temporal regulation.
format	article
author	Jason Z Zhang Andy H Nguyen Shigeki Miyamoto Joan Heller Brown Andrew D McCulloch Jin Zhang
author_facet	Jason Z Zhang Andy H Nguyen Shigeki Miyamoto Joan Heller Brown Andrew D McCulloch Jin Zhang
author_sort	Jason Z Zhang
title	Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.
title_short	Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.
title_full	Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.
title_fullStr	Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.
title_full_unstemmed	Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.
title_sort	histamine-induced biphasic activation of rhoa allows for persistent rhoa signaling.
publisher	Public Library of Science (PLoS)
publishDate	2020
url	https://doaj.org/article/0ebb54bacf2e4652ac3dc47d3752c53f
work_keys_str_mv	AT jasonzzhang histamineinducedbiphasicactivationofrhoaallowsforpersistentrhoasignaling AT andyhnguyen histamineinducedbiphasicactivationofrhoaallowsforpersistentrhoasignaling AT shigekimiyamoto histamineinducedbiphasicactivationofrhoaallowsforpersistentrhoasignaling AT joanhellerbrown histamineinducedbiphasicactivationofrhoaallowsforpersistentrhoasignaling AT andrewdmcculloch histamineinducedbiphasicactivationofrhoaallowsforpersistentrhoasignaling AT jinzhang histamineinducedbiphasicactivationofrhoaallowsforpersistentrhoasignaling
_version_	1718375883407884288

Histamine-induced biphasic activation of RhoA allows for persistent RhoA signaling.

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