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Updated: Jun 17, 2025

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
Published on: December 9, 2022
Cullin 3/with No Lysine [K] Kinase/Ste20/SPS-Related Proline Alanine Rich Kinase Signaling: Impact on NaCl
Kingsley Omage1, James A McCormick
1Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon.
Abstract:
The sodium chloride cotransporter (NCC) fine-tunes Na + balance and indirectly affects the homeostasis of other ions including K + , Mg 2+ , and Ca 2+ . Owing to its effects on Na + balance, BP is significantly affected by alterations in NCC activity. Several factors have been reported to influence the expression and activity of NCC. One critical factor is NCC phosphorylation/dephosphorylation that occurs at key serine-threonine amino acid residues of the protein. Phosphorylation, which results in increased NCC activity, is mediated by the with no lysine [K] (WNK)-SPS-related proline alanine rich kinase (SPAK)/OSR1 kinases. NCC activation stimulates reabsorption of Na + , increasing extracellular fluid volume and hence BP. On the other hand, proteasomal degradation of WNK kinases after ubiquitination by the Cullin 3-Kelch-like 3 E3 ubiquitin ligase complex and dephosphorylation pathways oppose WNK-SPAK/OSR1-mediated NCC activation. Components of the Cullin 3/Kelch-like 3-WNK-SPAK/OSR1 regulatory pathway may be targets for novel antihypertensive drugs. In this review, we outline the impact of these regulators on the activity of NCC and the consequent effect on BP.
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