SMURF1/2 Are Novel Regulators of WNK1 Stability.

Kinases and phosphatases Pub Date : 2024-09-01 Epub Date: 2024-09-20 DOI:10.3390/kinasesphosphatases2030019
Ankita B Jaykumar, Sakina Plumber, Derk Binns, Chonlarat Wichaidit, Katherine Luby-Phelps, Melanie H Cobb
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引用次数: 0

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-β). We have previously reported crosstalk between TGF-β 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 the 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-β 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-β receptor levels, in turn, controlling TGF-β signaling.

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SMURF1/2是WNK1稳定性的新调控因子。
血管生成对现有血管的重塑和修复至关重要,这一过程需要包括转化生长因子β (TGF-β)控制的信号通路。我们之前报道了TGF-β和无赖氨酸(K) 1蛋白激酶(WNK1)之间的串扰。编码WNK1基因的纯合子破坏会导致胚胎期E12小鼠因血管生成受损而死亡,这种缺陷可以通过激活形式的WNK1底物激酶氧化应激反应1 (OSR1)的内皮特异性表达来修复。然而,通过TGF-β和WNK1/OSR1之间的合作调节的分子过程尚不清楚。在这里,我们发现WNK1与E3泛素连接酶SMURF1/2相互作用。此外,我们发现WNK1调节SMURF1/2蛋白的稳定性,反之亦然。我们还证明WNK1活性调节TGF-β受体水平,进而控制TGF-β信号传导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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