Osmotic stress induces the phosphorylation of WNK4 Ser575 via the p38MAPK-MK pathway
| Autor: | Jun-ichi Maruyama, Yumie Kobayashi, Kohsuke Takeda, Tsuyoshi Umeda, Isao Naguro, Hidenori Ichijo, Alain Vandewalle |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Osmotic shock Gene Expression Protein Serine-Threonine Kinases p38 Mitogen-Activated Protein Kinases Article Cell Line 03 medical and health sciences 0302 clinical medicine Osmotic Pressure Humans Medicine ASK1 Amino Acids Phosphorylation Protein kinase A Adaptor Proteins Signal Transducing Multidisciplinary MAP kinase kinase kinase urogenital system business.industry Kinase Microfilament Proteins MAP Kinase Kinase Kinases WNK4 Cell biology Enzyme Activation 030104 developmental biology Biochemistry Signal transduction Carrier Proteins business 030217 neurology & neurosurgery Protein Binding Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep18710 |
| Popis: | The With No lysine [K] (WNK)-Ste20-related proline/alanine-rich kinase (SPAK)/oxidative stressresponsive 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. Scientific Reports, 6, 18710; 2016 |
| Databáze: | OpenAIRE |
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