Serum- and glucocorticoid-induced protein kinase 1 (SGK1) increases the cystic fibrosis transmembrane conductance regulator (CFTR) in airway epithelial cells by phosphorylating Shank2E protein.

ABSTRACT: The glucocorticoid dexamethasone increases cystic fibrosis transmembrane conductance regulator (CFTR) abundance in human airway epithelial cells by a mechanism that requires serum- and glucocorticoid-induced protein kinase 1 (SGK1) activity. The goal of this study was to determine whether SGK1 increases CFTR abundance by phosphorylating Shank2E, a PDZ domain protein that contains two SGK1 phosphorylation consensus sites. We found that SGK1 phosphorylates Shank2E as well as a peptide containing the first SGK1 consensus motif of Shank2E. The dexamethasone-induced increase in CFTR abundance was diminished by overexpression of a dominant-negative Shank2E in which the SGK1 phosphorylation sites had been mutated. siRNA-mediated reduction of Shank2E also reduced the dexamethasone-induced increase

SUBMITTER: Koeppen K 

PROVIDER: S-EPMC4059155 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature