SGK Kinases and Their Role in Epithelial Transport

Abstract

The serum/glucocorticoid-induced kinase Sgk1 plays an important role in the regulation of epithelial ion transport. This kinase is very rapidly regulated at the transcriptional level as well as via posttranslational modifications involving phosphorylation by the MAP or PI-3 kinase pathways and/or ubiquitylation. Although Sgk1 is a cell survival kinase, its primary role likely concerns the regulation of epithelial ion transport, as suggested by the phenotype of Sgk1-null mice, which display a defect in Na( homeostasis owing to disturbed renal tubular Na+ handling. In this review we first discuss the molecular, cellular, and regulatory aspects of Sgk1 and its paralogs. We then discuss its roles in the physiology and pathophysiology of epithelial ion transport.

Serum/glucocorticoid-induced protein kinase-1 facilitates androgen receptor-dependent cell survival

“…The distal promoter 2252-SEAP (À3382/À1130) and its truncated one 442-SEAP (À3382/À2940) contain several putative SRE motifs, as suggested by a computer-based inspection. 19 The androgen responsiveness of these reporters was analyzed in LNCaP and LAPC-4 cells. As shown in Figure 2d and e, R1881 treatment significantly activated the reporters driven by the proximal (1258-SEAP) and distal (2252-SEAP) promoter fragments in both cell lines.…”

“…The secondary ARE-2 motif resides in the far distal region of the sgk1 gene promoter, as proposed by others previously. 19 SGK-1 is required for AR-dependent survival. Similar to Akt, SGK-1 has been shown to be a cellular survival factor.…”

“…In fact, like Akt, SGK-1 is activated by phosphorylation through a phosphatidylinositol 3-kinase (PI3K)-dependent signal pathway. 18,19 However, unlike other protein kinases in AGC family, such as Akt, SGK-1 but not SGK-2 or -3 is regulated and activated mainly through a transcriptional mechanism by extracellular stimuli. Its promoter contains several consensus sequences for transcription factors that can be activated by a very large spectrum of stimuli besides glucocorticoid and serum.…”

“…Its promoter contains several consensus sequences for transcription factors that can be activated by a very large spectrum of stimuli besides glucocorticoid and serum. 19,20 Upon induction, it acts as a cell survival factor in different situations and is also able to regulate numerous membrane transporters and channel proteins. 18,19 In the studies reported here we identified a downstream effecter pathway responsible for AR-dependent survival.…”

“…19,20 Upon induction, it acts as a cell survival factor in different situations and is also able to regulate numerous membrane transporters and channel proteins. 18,19 In the studies reported here we identified a downstream effecter pathway responsible for AR-dependent survival. We found that expression of SGK-1 but not other isoforms or Akt was upregulated by androgen stimulation.…”