Figure 3.

Nedd4-2 function in regulating epithelial sodium channel (ENaC). Nedd4-2 has been shown to bind directly with and ubiquitylate ENaC, and disruption of this interaction leads to increased ENaC surface expression and activity, as seen in Liddle’s syndrome. Nedd4-2 is (in part) the converging point for both aldosterone and insulin signals, mediated through Sgk1 (serum glucocorticoid-inducible kinase) and Akt (also called protein kinase B, PKB), respectively. Phosphorylated Nedd4-2 can bind to 14-3-3, a phospho-protein binding protein, which inhibits the interaction between Nedd4-2 and ENaC