ArticleProceedings of the National Academy of Sciences of the United States of America2013
Regulation of OSR1 and the sodium, potassium, two chloride cotransporter by convergent signals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed, 34 citations in OpenAlex.
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- Apolipoprotein-L1 G1 variant contributes to hydrocephalus but not to atherosclerosis in apolipoprotein-E knock-out mice.Clinical science (London, England : 1979) · 2025Article
- Chloride deregulation and GABA depolarization in MTOR-related malformations of cortical development.Brain : a journal of neurology · 2025Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Article
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- UBR5 is a novel regulator of WNK1 stability.American journal of physiology. Cell physiology · 2022Article
- WNK1 Enhances Migration and Invasion in Breast Cancer Models.Molecular cancer therapeutics · 2021Article
- Pro-Resolving FPR2 Agonists Regulate NADPH Oxidase-Dependent Phosphorylation of HSP27, OSR1, and MARCKS and Activation of the Respective Upstream Kinases.Antioxidants (Basel, Switzerland) · 2021Article
- Synovial Fluid of Patient With Rheumatoid Arthritis Enhanced Osmotic Sensitivity Through the Cytotoxic Edema Module in Synoviocytes.Frontiers in cell and developmental biology · 2021Article
- Article
- Phosphoproteomic analysis sheds light on intracellular signaling cascades triggered by Formyl-Peptide Receptor 2.Scientific reports · 2019Article
- Therapeutic Suppression of mTOR (Mammalian Target of Rapamycin) Signaling Prevents and Reverses Salt-Induced Hypertension and Kidney Injury in Dahl Salt-Sensitive Rats.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Lysosome: The metabolic signaling hub.Traffic (Copenhagen, Denmark) · 2019Review
- mTOR as a central hub of nutrient signalling and cell growth.Nature cell biology · 2019Review
- Hypertension: the missing WNKs.American journal of physiology. Renal physiology · 2016Review
- The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging.Cell metabolism · 2016Review
- Generation of WNK1 knockout cell lines by CRISPR/Cas-mediated genome editing.American journal of physiology. Renal physiology · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The Ste20 family protein kinases oxidative stress-responsive 1 (OSR1) and the STE20/SPS1-related proline-, alanine-rich kinase directly regulate the solute carrier 12 family of cation-chloride cotransporters and thereby modulate a range of processes including cell volume homeostasis, blood pressure, hearing, and kidney function. OSR1 and STE20/SPS1-related proline-, alanine-rich kinase are activated by with no lysine [K] protein kinases that phosphorylate the essential activation loop regulatory site on these kinases. We found that inhibition of phosphoinositide 3-kinase (PI3K) reduced OSR1 activation by osmotic stress. Inhibition of the PI3K target pathway, the mammalian target of rapamycin complex 2 (mTORC2), by depletion of Sin1, one of its components, decreased activation of OSR1 by sorbitol and reduced activity of the OSR1 substrate, the sodium, potassium, two chloride cotransporter, in HeLa cells. OSR1 activity was also reduced with a pharmacological inhibitor of mTOR. mTORC2 phosphorylated OSR1 on S339 in vitro, and mutation of this residue eliminated OSR1 phosphorylation by mTORC2. Thus, we identify a previously unrecognized connection of the PI3K pathway through mTORC2 to a Ste20 protein kinase and ion homeostasis.
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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.