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bioRxiv · 10.1101/2024.07.31.606092

SMURF1/2 are novel regulators of WNK1 stability

Jaykumar, A. B.·Plumber, S.·Binns, D.·Wichaidit, C.·Luby-Phelps, K.·Cobb, M. H.
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Abstract

Angiogenesis is essential for remodeling and repairing existing vessels, and this process requires signaling pathways including those controlled by transforming growth factor beta (TGF-{beta}). We have previously reported crosstalk between TGF-{beta} and the protein kinase With No lysine (K) 1 (WNK1). Homozygous disruption of the gene encoding WNK1 results in lethality in mice near embryonic day E12 due to impaired angiogenesis and this defect can be rescued by endothelial-specific expression of an activated form of the WNK1 substrate kinase Oxidative Stress-Responsive 1 (OSR1). However, molecular processes regulated via a collaboration between TGF-{beta} and WNK1/OSR1 are not well understood. Here we show that WNK1 interacts with the E3 ubiquitin ligases SMURF1/2. In addition, we discovered that WNK1 regulates SMURF1/2 protein stability and vice versa. We also demonstrate that WNK1 activity regulates TGF-{beta} receptor levels, in turn, controlling TGF-{beta} signaling.

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Jaykumar, A. B., Plumber, S., Binns, D., Wichaidit, C., Luby-Phelps, K., Cobb, M. H.. 2024-08-01. SMURF1/2 are novel regulators of WNK1 stability. https://doi.org/10.1101/2024.07.31.606092

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