Crosstalk between phosphorylation and ubiquitination is involved in high salt-induced WNK4 expression

Zhao,Xiaoyue; Lai,Guangrui; Tu,Jianqiao; Liu,Shuchang; Zhao,Yanyan

doi:10.3892/etm.2020.9565

Crosstalk between phosphorylation and ubiquitination is involved in high salt-induced WNK4 expression

Authors:
- Xiaoyue Zhao
- Guangrui Lai
- Jianqiao Tu
- Shuchang Liu
- Yanyan Zhao
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Affiliations: Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110003, P.R. China
Published online on: December 10, 2020 https://doi.org/10.3892/etm.2020.9565
Article Number: 133

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Abstract

With no lysine 4 (WNK4) is a serine/threonine kinase, which is expressed in the kidney and associated with salt-sensitive hypertension. However, how salt regulates WNK4 remains unclear. In the present study, the C57BL/6 mice and HEK293 cells were treated with high salt and the expression of WNK4 protein and its ubiquitination and phosphorylation levels were detected. Western blotting demonstrated that WNK4 expression was significantly increased in high salt-treated mice and cells. Meanwhile, co-immunoprecipitation analysis demonstrated that the ubiquitination of WNK4 was decreased under high-salt simulation. It was also identified that the Lys-1023 site was the most important ubiquitination site for WNK4, and it was found that phosphorylation at the Ser-1022 site was a prerequisite for ubiquitination. These results suggested that there was crosstalk between phosphorylation and ubiquitination in the WNK4 protein, and high salt may downregulate its phosphorylation and, in turn, decrease its ubiquitination, leading to a decrease in WNK4 degradation. This eventually resulted in an increase in the abundance of WNK4 protein.

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