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Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway

The With No lysine [K] (WNK)-Ste20-related proline/alanine-rich kinase (SPAK)/oxidative stress-responsive kinase 1 (OSR1) pathway has been reported to be a crucial signaling pathway for triggering pseudohypoaldosteronism type II (PHAII), an autosomal dominant hereditary disease that is characterized...

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Autores principales: Maruyama, Junichi, Kobayashi, Yumie, Umeda, Tsuyoshi, Vandewalle, Alain, Takeda, Kohsuke, Ichijo, Hidenori, Naguro, Isao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702109/
https://www.ncbi.nlm.nih.gov/pubmed/26732173
http://dx.doi.org/10.1038/srep18710
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author Maruyama, Junichi
Kobayashi, Yumie
Umeda, Tsuyoshi
Vandewalle, Alain
Takeda, Kohsuke
Ichijo, Hidenori
Naguro, Isao
author_facet Maruyama, Junichi
Kobayashi, Yumie
Umeda, Tsuyoshi
Vandewalle, Alain
Takeda, Kohsuke
Ichijo, Hidenori
Naguro, Isao
author_sort Maruyama, Junichi
collection PubMed
description The With No lysine [K] (WNK)-Ste20-related proline/alanine-rich kinase (SPAK)/oxidative stress-responsive kinase 1 (OSR1) pathway has been reported to be a crucial signaling pathway for triggering pseudohypoaldosteronism type II (PHAII), an autosomal dominant hereditary disease that is characterized by hypertension. However, the molecular mechanism(s) by which the WNK-SPAK/OSR1 pathway is regulated remain unclear. In this report, we identified WNK4 as an interacting partner of a recently identified MAP3K, apoptosis signal-regulating kinase 3 (ASK3). We found that WNK4 is phosphorylated in an ASK3 kinase activity-dependent manner. By exploring the ASK3-dependent phosphorylation sites, we identified Ser575 as a novel phosphorylation site in WNK4 by LC-MS/MS analysis. ASK3-dependent WNK4 Ser575 phosphorylation was mediated by the p38MAPK-MAPK-activated protein kinase (MK) pathway. Osmotic stress, as well as hypotonic low-chloride stimulation, increased WNK4 Ser575 phosphorylation via the p38MAPK-MK pathway. ASK3 was required for the p38MAPK activation induced by hypotonic stimulation but was not required for that induced by hypertonic stimulation or hypotonic low-chloride stimulation. Our results suggest that the p38MAPK-MK pathway might regulate WNK4 in an osmotic stress-dependent manner but its upstream regulators might be divergent depending on the types of osmotic stimuli.
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spelling pubmed-47021092016-01-14 Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway Maruyama, Junichi Kobayashi, Yumie Umeda, Tsuyoshi Vandewalle, Alain Takeda, Kohsuke Ichijo, Hidenori Naguro, Isao Sci Rep Article The With No lysine [K] (WNK)-Ste20-related proline/alanine-rich kinase (SPAK)/oxidative stress-responsive kinase 1 (OSR1) pathway has been reported to be a crucial signaling pathway for triggering pseudohypoaldosteronism type II (PHAII), an autosomal dominant hereditary disease that is characterized by hypertension. However, the molecular mechanism(s) by which the WNK-SPAK/OSR1 pathway is regulated remain unclear. In this report, we identified WNK4 as an interacting partner of a recently identified MAP3K, apoptosis signal-regulating kinase 3 (ASK3). We found that WNK4 is phosphorylated in an ASK3 kinase activity-dependent manner. By exploring the ASK3-dependent phosphorylation sites, we identified Ser575 as a novel phosphorylation site in WNK4 by LC-MS/MS analysis. ASK3-dependent WNK4 Ser575 phosphorylation was mediated by the p38MAPK-MAPK-activated protein kinase (MK) pathway. Osmotic stress, as well as hypotonic low-chloride stimulation, increased WNK4 Ser575 phosphorylation via the p38MAPK-MK pathway. ASK3 was required for the p38MAPK activation induced by hypotonic stimulation but was not required for that induced by hypertonic stimulation or hypotonic low-chloride stimulation. Our results suggest that the p38MAPK-MK pathway might regulate WNK4 in an osmotic stress-dependent manner but its upstream regulators might be divergent depending on the types of osmotic stimuli. Nature Publishing Group 2016-01-06 /pmc/articles/PMC4702109/ /pubmed/26732173 http://dx.doi.org/10.1038/srep18710 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Maruyama, Junichi
Kobayashi, Yumie
Umeda, Tsuyoshi
Vandewalle, Alain
Takeda, Kohsuke
Ichijo, Hidenori
Naguro, Isao
Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
title Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
title_full Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
title_fullStr Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
title_full_unstemmed Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
title_short Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
title_sort osmotic stress induces the phosphorylation of wnk4 ser575 via the p38mapk-mk pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702109/
https://www.ncbi.nlm.nih.gov/pubmed/26732173
http://dx.doi.org/10.1038/srep18710
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