ArticleJCI insight2020
WNK1 regulates uterine homeostasis and its ability to support pregnancy.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Cuproptosis and Mitophagy Mediated by the THUMPD1/IGF2R-Dependent Suppression of AKT and Activation of AMPK Signaling Suppress Lung Adenocarcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- STK39 inhibits antiviral immune response by inhibiting DCAF1-mediated PP2A degradation.Acta pharmaceutica Sinica. B · 2025Article
- Effect of Propolis on PPP2R1A and Apoptosis in Cancer Cells.Biochemistry research international · 2025Article
- Zebrafish model for functional screening of flow-responsive genes controlling endothelial cell proliferation.Scientific reports · 2024Article
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Chemokine-mediated F-actin dynamics, polarity, and migration in B lymphocytes depend on WNK1 signaling.Science signaling · 2024Article
- Focal adhesion kinase confers lenvatinib resistance in hepatocellular carcinoma via the regulation of lysine-deficient kinase 1.Molecular carcinogenesis · 2024Article
- Inhibition of WNK Kinases in NK Cells Disrupts Cellular Osmoregulation and Control of Tumor Metastasis.Journal of innate immunity · 2024Article
- WNK1 is required during male pachynema to sustain fertility.iScience · 2023Article
- Article
- WNK1-OSR1 Signaling Regulates Angiogenesis-Mediated Metastasis towards Developing a Combinatorial Anti-Cancer Strategy.International journal of molecular sciences · 2022Article
- Myometrial progesterone receptor determines a transcription program for uterine remodeling and contractions during pregnancy.PNAS nexus · 2022Article
- Regulation of AKT Signaling in Mouse Uterus.Endocrinology · 2022Article
- Targeting Akt in cancer for precision therapy.Journal of hematology & oncology · 2021Review
- Progesterone receptor isoform B regulates theProceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
WNK1 (with no lysine [K] kinase 1) is an atypical kinase protein ubiquitously expressed in humans and mice. A mutation in its encoding gene causes hypertension in humans, which is associated with abnormal ion homeostasis. WNK1 is critical for in vitro decidualization in human endometrial stromal cells, thereby demonstrating its importance in female reproduction. Using a mouse model, WNK1 was ablated in the female reproductive tract to define its in vivo role in uterine biology. Loss of WNK1 altered uterine morphology, causing endometrial epithelial hyperplasia, adenomyotic features, and a delay in embryo implantation, ultimately resulting in compromised fertility. Combining transcriptomic, proteomic, and interactomic analyses revealed a potentially novel regulatory pathway whereby WNK1 represses AKT phosphorylation through protein phosphatase 2A (PP2A) in endometrial cells from both humans and mice. We show that WNK1 interacted with PPP2R1A, the alpha isoform of the PP2A scaffold subunit. This maintained the levels of PP2A subunits and stabilized its activity, which then dephosphorylated AKT. Therefore, loss of WNK1 reduced PP2A activity, causing AKT hypersignaling. Using FOXO1 as a readout of AKT activity, we demonstrate that there was escalated FOXO1 phosphorylation and nuclear exclusion, leading to a disruption in the expression of genes that are crucial for embryo implantation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.