ArticleJournal of the American Society of Nephrology : JASN2011
Activation of PI3-kinase stimulates endocytosis of ROMK via Akt1/SGK1-dependent phosphorylation of WNK1.
Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 68 citations in OpenAlex.
- Characterizing risk groups in papillary thyroid carcinoma through T-Cell mediated tumor cell killing-related genes: a pathway to therapeutic predictions.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- WNKs regulate mouse behavior and alter central nervous system glucose uptake and insulin signaling.bioRxiv : the preprint server for biology · 2025Article
- Case Report: The long-term effects of the empagliflozin therapy on glycemia and renal function in a patient with Rabson-Mendenhall syndrome caused by two heterozygous variants in INSR gene.Frontiers in endocrinology · 2025Article
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Monocarboxylate transporter 4 promotes the migration of non‑cancerous L929 fibroblast cells by activating the IGF1/IGF1R/PIK3R3/SGK1 axis.Oncology letters · 2023Article
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (CASP1) modulation by intracellular ClImmunology · 2021Article
- Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.Molecular cell · 2020Article
- The TRPV4 Agonist GSK1016790A Regulates the Membrane Expression of TRPV4 Channels.Frontiers in pharmacology · 2019Article
- WNK pathways in cancer signaling networks.Cell communication and signaling : CCS · 2018Review
- WNK1 kinase is essential for insulin-stimulated GLUT4 trafficking in skeletal muscle.FEBS open bio · 2018Article
- Progesterone Receptor Regulation of Uterine Adaptation for Pregnancy.Trends in endocrinology and metabolism: TEM · 2018Review
- WNK1 kinase and its partners Akt, SGK1 and NBC-family NaOncotarget · 2018Article
- WNK1 is required for proliferation induced by hypotonic challenge in rat vascular smooth muscle cells.Acta pharmacologica Sinica · 2018Article
- WNK lysine deficient protein kinase 1 regulates human endometrial stromal cell decidualization, proliferation, and migration in part through mitogen-activated protein kinase 7.Biology of reproduction · 2017Article
- Emerging Targets of Diuretic Therapy.Clinical pharmacology and therapeutics · 2017Review
- Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium Depletion.Journal of the American Society of Nephrology : JASN · 2017Article
- Downregulation of ACSM3 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma.American journal of cancer research · 2017Article
- Multistep regulation of autophagy by WNK1.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- WNK1 kinase balances T cell adhesion versus migration in vivo.Nature immunology · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
WNK kinases stimulate endocytosis of ROMK channels to regulate renal K+ handling. Phosphatidylinositol 3-kinase (PI3K)-activating hormones, such as insulin and IGF 1, phosphorylate WNK1, but how this affects the regulation of ROMK abundance is unknown. Here, serum starvation of ROMK-transfected HEK cells led to an increase of ROMK current density; subsequent addition of insulin or IGF1 inhibited ROMK currents in a PI3K-dependent manner. Serum and insulin also increased phosphorylation of the downstream kinases Akt1 and SGK1 as well as WNK1. A biotinylation assay suggested that insulin and IGF1 inhibit ROMK by enhancing its endocytosis, a process that WNK1 may mediate. Knockdown of WNK1 with siRNA or expression of a phospho-deficient WNK1 mutant (T58A) both prevented insulin-induced inhibition of ROMK currents, suggesting that phosphorylation at Threonine-58 of WNK1 is important to mediate the inhibition of ROMK by PI3K-activating hormones or growth factors. In vitro and in vivo kinase assays supported the notion that Akt1 and SGK1 can phosphorylate WNK1 at this site, and we established that Akt1 and SGK1 synergistically inhibit ROMK through WNK1. We used dominant-negative intersectin and dynamin constructs to show that SGK1-mediated phosphorylation of WNK1 inhibits ROMK by promoting its endocytosis. Taken together, these results suggest that PI3K-activating hormones inhibit ROMK by enhancing its endocytosis via a mechanism that involves phosphorylation of WNK1 by Akt1 and SGK1.
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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.