ArticleScience signaling2014
Chloride sensing by WNK1 involves inhibition of autophosphorylation.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 241 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
241 citing papers in PubMed, 398 citations in OpenAlex.
- Hypotonicity-Induced WNK1 Phosphorylation Prevents HBasic & clinical pharmacology & toxicology · 2026Article
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- An All-Optical Approach to Probe Chloride Transport with a Bright ChlorON.bioRxiv : the preprint server for biology · 2026Article
- Monogenic Kidney Disorders as Hidden Drivers of Electrolyte Imbalance and Hypertension.Electrolyte & blood pressure : E & BP · 2026Review
- WNK1 Phosphorylation Sites in TBC1D1 and TBC1D4 Modulate Cell-Surface Abundance of GLUT1.Cells · 2026Article
- Exploring the Role of the SLC12A Cation-Coupled Chloride Cotransporters in the Cardiovascular System.Cells · 2026Review
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- Association of Serum Chloride Concentration With All-Cause and Cardiovascular Mortality in Patients Undergoing Peritoneal Dialysis: The Fukuoka Peritoneal Dialysis Registry.Kidney medicine · 2026Article
- WNK-SPAK-NKCC1/KCC2 pathway disrupts chloride homeostasis and drives hyperactivation of PVN-CRH neurons in essential hypertension.iScience · 2026Article
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Structural Basis for Potassium Inhibition of WNK Kinases.Biochemistry · 2026Article
- Hypochloraemia independently associates with short-term mortality in patients with acute heart failure: a study from Vietnam.Open heart · 2026Article
- Potassium and the kidney.Nature reviews. Nephrology · 2026Review
- LRRC8A-containing anion channels promote glioblastoma proliferation via a WNK1/mTORC2-dependent mechanism.The Journal of physiology · 2026Article
- Use of acetazolamide in volume overload: start at the beginning.Clinical kidney journal · 2026Review
- Functional Nano-segregation of Distinct Forms of Neurotransmission.Advances in neurobiology · 2026Review
- Pancreatitis: correcting CFTR expression and function as a promising effective treatment.Frontiers in physiology · 2026Review
- Initial serum chloride is associated with all-cause mortality in critically ill patients with acute kidney injury.Renal failure · 2025Article
- Central Osmolality Sensing for Arginine Vasopressin Release Is Mediated by WNK1-OSR1/SPAK-Kv3.1 Cascade.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Machine learning models predict mortality risk in diabetic neuropathy patients using MIMIC-IV data.Scientific reports · 2025Article
181 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension. WNK1 is at the top of a kinase cascade, leading to phosphorylation of several cotransporters, in particular those transporting sodium, potassium, and chloride (NKCC), sodium and chloride (NCC), and potassium and chloride (KCC). The responsiveness of NKCC, NCC, and KCC to changes in extracellular chloride parallels their phosphorylation state, provoking the proposal that these transporters are controlled by a chloride-sensitive protein kinase. We found that chloride stabilizes the inactive conformation of WNK1, preventing kinase autophosphorylation and activation. Crystallographic studies of inactive WNK1 in the presence of chloride revealed that chloride binds directly to the catalytic site, providing a basis for the unique position of the catalytic lysine. Mutagenesis of the chloride-binding site rendered the kinase less sensitive to inhibition of autophosphorylation by chloride, validating the binding site. Thus, these data suggest that WNK1 functions as a chloride sensor through direct binding of a regulatory chloride ion to the active site, which inhibits autophosphorylation.
Indexed as
Identifiers
What OpenQuestion holds
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.