| Autor: |
Inglis, S. K., Gallacher, M., Brown, S. G., McTavish, N., Getty, J., Husband, E. M., Murray, J. T., Wilson, S. M. |
| Předmět: |
|
| Zdroj: |
Pflügers Archiv: European Journal of Physiology; Mar2009, Vol. 457 Issue 6, p1287-1301, 15p, 8 Graphs |
| Abstrakt: |
Studies of HeLa cells and serum- and glucocorticoid-regulated kinase 1 (SGK1) knockout mice identified threonine residues in the n- myc downstream-regulated gene 1 protein (NDRG1-Thr346/356/366) that are phosphorylated by SGK1 but not by related kinases (Murray et al., Biochem J 385:1–12, ). We have, therefore, monitored the phosphorylation of NDRG1-Thr346/356/366 in order to explore the changes in SGK1 activity associated with the induction and regulation of the glucocorticoid-dependent Na+ conductance ( GNa) in human airway epithelial cells. Transient expression of active (SGK1-S422D) and inactive (SGK1-K127A) SGK1 mutants confirmed that activating SGK1 stimulates NDRG1-Thr346/356/366 phosphorylation. Although GNa is negligible in hormone-deprived cells, these cells displayed basal SGK1 activity that was sensitive to LY294002, an inhibitor of 3-phosphatidylinositol phosphate kinase (PI3K). Dexamethasone (0.2 μM) acutely activated SGK1 and the peak of this response (2–3 h) coincided with the induction of GNa, and both responses were PI3K-dependent. While these data suggest that SGK1 might mediate the rise in GNa, transient expression of the inactive SGK1-K127A mutant did not affect the hormonal induction of GNa but did suppress the activation of SGK1. Dexamethasone-treated cells grown on permeable supports formed confluent epithelial sheets that generated short circuit current due to electrogenic Na+ absorption. Forskolin and insulin both stimulated this current and the response to insulin, but not forskolin, was LY294002-sensitive and associated with the activation of SGK1. While these data suggest that SGK1 is involved in the control of GNa, its role may be minor, which could explain why sgk1 knockout has different effects upon different tissues. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
Full text from SpringerLink