2016年1月
Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
SCIENTIFIC REPORTS
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- 巻
- 6
- 号
- 開始ページ
- 18710
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/srep18710
- 出版者・発行元
- NATURE PUBLISHING GROUP
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.
- リンク情報
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- DOI
- https://doi.org/10.1038/srep18710
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201702208114767128
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/26732173
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000368656200001&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1038/srep18710
- ISSN : 2045-2322
- J-Global ID : 201702208114767128
- PubMed ID : 26732173
- Web of Science ID : WOS:000368656200001