The physiological impact of the serum and glucocorticoid-inducible kinase SGK1.
OBJECTIVE
The role of serum and glucocorticoid-inducible kinase 1 (SGK1) in renal physiology and pathophysiology is reviewed with particular emphasis on recent advances.


RESULTS
The mammalian target of rapamycin complex 2 has been shown to phosphorylate SGK1 at Ser422 (the so-called hydrophobic motif). Ser397 and Ser401 are two additional SGK1-phosphorylation sites required for maximal SGK1 activity. A 5' variant alternate transcript of human Sgk1 has been identified that is widely expressed and shows improved stability, enhanced membrane association, and greater stimulation of epithelial Na+ transport. SGK1 is essential for optimal processing of the epithelial sodium channel and also regulates the expression of the Na+-Cl- cotransporter. With regard to pathophysiology, SGK1 participates in the stimulation of renal tubular glucose transport in diabetes, the renal profibrotic effect of both angiotensin II and aldosterone, and in fetal programing of arterial hypertension.


CONCLUSIONS
The outlined recent findings advanced our understanding of the molecular regulation of SGK1 as well as the role of the kinase in renal physiology and the pathophysiology of renal disease and hypertension. Future studies using pharmacological inhibitors of SGK1 will reveal the utility of the kinase as a new therapeutic target.
Lang
Florian
F
Department of Physiology, University of Tuebingen, Gmelinstrasse 5, Tuebingen 72076, Germany. florian.lang@uni-tuebingen.de
Artunc
Ferruh
F
Vallon
Volker
V
D000818:Animals; D001066:Appetite / Q000235:genetics / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000502:physiology; D024821:Metabolic Syndrome / Q000201:enzymology / Q000235:genetics; D009765:Obesity / Q000201:enzymology / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics / Q000502:physiology*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases