1. A working model for NCC regulation through the WNK-SPAK/OSR1 signaling cascade.
A working model for NCC regulation through the WNK-SPAK/OSR1 signaling cascade. To date, a number of hormones have been shown to stimulate NCC phosphorylation at residues that are directly phosphorylated by SPAK and OSR1. These include aldosterone, angiotensin II, insulin, and vasopressin. Tacrolimus also enhances NCC phosphorylation at these sites, resulting in thiazide-sensitive NaCl reabsorption. In all cases, the mechanism likely involves hormonal activation of WNKs, which in turn, activates SPAK/OSR1. In some cases, such as aldosterone (66) and angiotensin II (58,64,65), hormone-induced changes in WNK-SPAK/OSR1-dependent signaling are also associated with increased trafficking of NCC to the plasma membrane.
Arohan R. Subramanya, and David H. Ellison CJASN 2014;9:
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