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. Author manuscript; available in PMC: 2018 Jul 1.
Published in final edited form as: Pediatr Nephrol. 2016 May 18;32(7):1109–1121. doi: 10.1007/s00467-016-3411-8

Figure 4.

Figure 4

WNK kinases stimulate vasoconstriction and NaCl reabsorption. WNK kinases phosphorylate and activate two related kinases, SPAK and OSR1. SPAK and OSR1 phosphorylate the N-terminus of the related sodium-coupled chloride cotransporters, NKCC1 in the vasculature, NCC in the distal convoluted tubule, and NKCC2 in the thick ascending limb of the loop of Henle. Phosphorylation results in transporter activation, leading to vasoconstriction and increased sodium chloride reabsorption in multiple nephron segments. In addition, WNKs have positive regulatory effects on pendrin in the β-intercalated cells and paracellular chloride transport in the ASDN, mediated by claudin-4, which again will increase renal sodium chloride reabsorption. The overall effect of WNK signaling is to promote vasoconstriction and NaCl reabsorption.

DCT: distal convoluted tubule, TAL: thick ascending limb, ASDN: aldosterone-sensitive distal nephron