ArticleProceedings of the National Academy of Sciences of the United States of America2016
Multistep regulation of autophagy by WNK1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Lysophagy protects against ANXA11 amyloid fibril toxicity and propagation in FTLD.Translational neurodegeneration · 2026Article
- AMPK-OXSR1 signaling coordinates proximal tubular sodium transport and is modulated by canagliflozin.Frontiers in endocrinology · 2026Article
- Article
- Kinase interaction analysis predicts actions of the WNK-OSR1/SPAK pathway.Communications biology · 2025Article
- WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain acute myeloid leukaemia growth.Nature communications · 2025Article
- WNK1-dependent water influx is required for CD4Nature communications · 2025Article
- Bilobalide Activates Autophagy and Enhances the Efficacy of Bone Marrow Mesenchymal Stem Cells on Spinal Cord Injury Via Upregulating FMRP to Promote WNK1 mRNA Decay.Neurochemical research · 2024Article
- Delayed vacuolation in mammalian cells caused by hypotonicity and ion loss.Scientific reports · 2024Article
- Article
- 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
- WNK1 controls endosomal trafficking through TRIM27-dependent regulation of actin assembly.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Selective dopaminergic vulnerability in Parkinson's disease: new insights into the role of DAT.Frontiers in neuroscience · 2023Review
- Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications.Acta pharmaceutica Sinica. B · 2022Review
- An update regarding the role of WNK kinases in cancer.Cell death & disease · 2022Review
- WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- UBR5 is a novel regulator of WNK1 stability.American journal of physiology. Cell physiology · 2022Article
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The with-no-lysine (K) (WNK) kinases are an atypical family of protein kinases that regulate ion transport across cell membranes. Mutations that result in their overexpression cause hypertension-related disorders in humans. Of the four mammalian WNKs, only WNK1 is expressed throughout the body. We report that WNK1 inhibits autophagy, an intracellular degradation pathway implicated in several human diseases. Using small-interfering RNA-mediated WNK1 knockdown, we show autophagosome formation and autophagic flux are accelerated. In cells with reduced WNK1, basal and starvation-induced autophagy is increased. We also show that depletion of WNK1 stimulates focal class III phosphatidylinositol 3-kinase complex (PI3KC3) activity, which is required to induce autophagy. Depletion of WNK1 increases the expression of the PI3KC3 upstream regulator unc-51-like kinase 1 (ULK1), its phosphorylation, and activation of the kinase upstream of ULK1, the AMP-activated protein kinase. In addition, we show that the N-terminal region of WNK1 binds to the UV radiation resistance-associated gene (UVRAG) in vitro and WNK1 partially colocalizes with UVRAG, a component of a PI3KC3 complex. This colocalization decreases upon starvation of cells. Depletion of the SPS/STE20-related proline-alanine-rich kinase, a WNK1-activated enzyme, also induces autophagy in nutrient-replete or -starved conditions, but depletion of the related kinase and WNK1 substrate, oxidative stress responsive 1, does not. These results indicate that WNK1 inhibits autophagy by multiple mechanisms.
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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.