Year: 2024
Type: article
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 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.
Source: Kinases and Phosphatases
Institution: The University of Texas Southwestern Medical Center
Language: English
Topic: TGF-β signaling in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,137
Awards: Laser Scanning Confocal for UT Southwestern Live Cell Imaging Facility, G1329875265, G1485334055, G1530479005, G2076737215, G2595216862, G2972759846, G3602727137, The role of WNK1/OSR1 in endothelial cell migration and angiogenesis, G428461830, G4484861044, G4599071890, G5831923886, G5903964500, G6464818906, G6783076163, G6787967075, Cancer Intervention and Prevention Discoveries Program, G9000095536, UT Southwestern NORC, UT Southwestern Medical Center Simmons Comprehensive Cancer Center
OpenAlex ID: W4402679869