Fig. 1: The mechanism diagrams of how SGK1 regulates sodium reabsorption by Nedd4L.

A Epithelial sodium channel (ENaC) can be degraded by Neuronal precursor cell expression developmentally downregulated 4-like (Nedd4L) to maintain sodium balance. B Serum and glucocorticoid-regulated kinase 1(SGK1) phosphorylates and inhibits Nedd4L which is an ubiquitin ligase, thereby failing to reduce the channel expression and stimulate ion channel degradation. The phosphorylation (mainly surrounding amino acids Ser444, Ser338) mediated by SGK1 induces the interaction of Nedd4L with members of the 14-3-3 protein family, which in turn disrupts the ubiquitination and degradation of ENaC by Nedd4L, ultimately leading to more sodium reabsorption.