ArticleAmerican journal of physiology. Renal physiology2012
Protein phosphatase 1 modulates the inhibitory effect of With-no-Lysine kinase 4 on ROMK channels.
Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Arginine vasopressin regulates the renal NaAmerican journal of physiology. Renal physiology · 2024Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Control of sodium and potassium homeostasis by renal distal convoluted tubules.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- L-WNK1 is required for BK channel activation in intercalated cells.American journal of physiology. Renal physiology · 2021Article
- WNK4 kinase: from structure to physiology.American journal of physiology. Renal physiology · 2021Review
- MST3 Involvement in NaInternational journal of molecular sciences · 2021Article
- Protein Phosphatase 1 Inhibitor-1 Mediates the cAMP-Dependent Stimulation of the Renal NaCl Cotransporter.Journal of the American Society of Nephrology : JASN · 2019Article
- C-terminally truncated, kidney-specific variants of the WNK4 kinase lack several sites that regulate its activity.The Journal of biological chemistry · 2018Article
- Phosphorylation by PKC and PKA regulate the kinase activity and downstream signaling of WNK4.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Serine/threonine phosphatases and aquaporin-2 regulation in renal collecting duct.American journal of physiology. Renal physiology · 2017Article
- Role and mechanisms of regulation of the basolateral KActa physiologica (Oxford, England) · 2017Review
- Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC.American journal of physiology. Renal physiology · 2016Article
- Regulation of the epithelial Na+ channel by the mTORC2/SGK1 pathway.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2016Review
- Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis.Kidney international · 2016Article
- Regulation of Potassium Homeostasis.Clinical journal of the American Society of Nephrology : CJASN · 2015Review
- Src-family protein tyrosine kinase phosphorylates WNK4 and modulates its inhibitory effect on KCNJ1 (ROMK).Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Dietary potassium and the renal control of salt balance and blood pressure.Pflugers Archiv : European journal of physiology · 2015Review
- Distal convoluted tubule.Comprehensive Physiology · 2015Review
- Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia.Cell metabolism · 2013Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
With-no-Lysine kinase 4 (WNK4) inhibited ROMK (Kir1.1) channels and the inhibitory effect of WNK4 was abolished by serum-glucocorticoid-induced kinase 1 (SGK1) but restored by c-Src. The aim of the present study is to explore the mechanism by which Src-family tyrosine kinase (SFK) modulates the effect of SGK1 on WNK4 and to test the role of SFK-WNK4-SGK1 interaction in regulating ROMK channels in the kidney. Immunoprecipitation demonstrated that protein phosphatase 1 (PP1) binds to WNK4 at amino acid (aa) residues 695-699 (PP1(#1)) and at aa 1211-1215 (PP1(#2)). WNK4(-PP1#1) and WNK4(-PP1#2), in which the PP1(#1) or PP1(#2) binding site was deleted or mutated, inhibited ROMK channels as potently as WNK4. However, c-Src restored the inhibitory effect of WNK4 but not WNK4(-PP1#1) on ROMK channels in the presence of SGK1. Moreover, expression of c-Src inhibited SGK1-induced phosphorylation of WNK4 but not WNK4(-PP1#1) at serine residue 1196 (Ser(1196)). In contrast, coexpression of c-Src restored the inhibitory effect of WNK4(-PP1#2) on ROMK in the presence of SGK1 and diminished SGK1-induced WNK4 phosphorylation at Ser(1196) in cells transfected with WNK4(-PP1#2). This suggests the possibility that c-Src regulates the interaction between WNK4 and SGK1 through activating PP1 binding to aa 695-9 thereby decreasing WNK4 phosphorylation and restoring the inhibitory effect of WNK4. This mechanism plays a role in suppressing ROMK channel activity during the volume depletion because inhibition of SFK or serine/threonine phosphatases increases ROMK channel activity in the cortical collecting duct of rats on a low-Na diet. We conclude that regulation of phosphatase activity by SFK plays a role in determining the effect of aldosterone on ROMK channels and on renal K secretion.
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