ArticleProceedings of the National Academy of Sciences of the United States of America2009
Src family protein tyrosine kinase (PTK) modulates the effect of SGK1 and WNK4 on ROMK channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- The endocytic adaptor ARH facilitates potassium conservation by regulating ROMK and BK.American journal of physiology. Renal physiology · 2025Article
- ENaC and ROMK activity are inhibited in the DCT2/CNT of TgWnk4American journal of physiology. Renal physiology · 2017Article
- 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
- Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport.Journal of the American Society of Nephrology : JASN · 2015Article
- 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
- WNK1 activates large-conductance Ca2+-activated K+ channels through modulation of ERK1/2 signaling.Journal of the American Society of Nephrology : JASN · 2015Article
- KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Distal convoluted tubule.Comprehensive Physiology · 2015Review
- MicroRNA-194 (miR-194) regulates ROMK channel activity by targeting intersectin 1.American journal of physiology. Renal physiology · 2014Article
- WNK4 inhibits Ca(2+)-activated big-conductance potassium channels (BK) via mitogen-activated protein kinase-dependent pathway.Biochimica et biophysica acta · 2013Article
- Src family protein tyrosine kinase regulates the basolateral K channel in the distal convoluted tubule (DCT) by phosphorylation of KCNJ10 protein.The Journal of biological chemistry · 2013Article
- Protein phosphatase 1 modulates the inhibitory effect of With-no-Lysine kinase 4 on ROMK channels.American journal of physiology. Renal physiology · 2012Article
- WNK kinases and the kidney.Experimental cell research · 2012Review
- Regulation of transport in the connecting tubule and cortical collecting duct.Comprehensive Physiology · 2012Review
- WNK4 kinase inhibits Maxi K channel activity by a kinase-dependent mechanism.American journal of physiology. Renal physiology · 2011Article
- MicroRNA 802 stimulates ROMK channels by suppressing caveolin-1.Journal of the American Society of Nephrology : JASN · 2011Article
- Angiotensin II diminishes the effect of SGK1 on the WNK4-mediated inhibition of ROMK1 channels.Kidney international · 2011Article
- The WNKs: atypical protein kinases with pleiotropic actions.Physiological reviews · 2011Review
- Regulation and function of potassium channels in aldosterone-sensitive distal nephron.Current opinion in nephrology and hypertension · 2010Review
- Multigene kinase network, kidney transport, and salt in essential hypertension.Kidney international · 2010Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
WNK4 (with no lysine kinase 4) inhibits ROMK channel activity in the distal nephron by stimulating clathrin-dependent endocytosis, an effect attenuated by SGK1 (serum-glucocorticoids-induced kinase)-mediated phosphorylation. It has been suggested that increased ROMK activity because of SGK1-mediated inhibition of WNK4 plays a role in promoting renal K secretion in response to elevated serum K or high K (HK) intake. In contrast, intravascular volume depletion also increases SGK1 activity but fails to stimulate ROMK channels and K secretion. Because HK intake decreases Src family protein tyrosine kinase (PTK) activity an inhibitor of ROMK channels, it is possible that Src family PTK may modulate the effects of SGK1 on WNK4. Here, we show that c-Src prevents SGK1 from attenuating WNK4's inhibition of ROMK activity. This effect of c-Src was WNK4-dependent because c-Src had no effect on ROMK harboring mutation at the site of c-Src phosphorylation (R1Y337A) in the absence of WNK4. Moreover, expression c-Src diminished the SGK1-mediated increase in serine phosphorylation of WNK4, suggesting that c-Src enhances WNK4-mediated inhibition of ROMK channels by suppressing the SGK1-induced phosphorylation. This notion is also supported by the observation that c-Src was not able to modulate the interaction between SGK1 and WNK4 mutants (WNK4(S1169A) or WNK4(S1169D)) in which an SGK1-phosphorylation site (serine 1169) was mutated by alanine or aspartate. We conclude that c-Src inhibits SGK1-mediated phosphorylation hereby restoring the WNK4-mediated inhibition of ROMK channels thus suppressing K secretion.
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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.