Serum- and glucocorticoid-inducible kinase 1 in the regulation of renal and extrarenal potassium transport.
Serum- and glucocorticoid inducible-kinase 1 (SGK1) is an early gene transcriptionally upregulated by cell stress such as cell shrinkage and hypoxia and several hormones including gluco- and mineralocorticoids. It is activated by insulin and growth factors. SGK1 is a powerful regulator of a wide variety of channels and transporters. The present review describes the role of SGK1 in the regulation of potassium (K(+)) channels, K(+) transporters and K(+) homeostasis. SGK1-regulated K(+) channels include renal outer medullary K+ channel, Kv1.3, Kv1.5, KCNE1/KCNQ1, KCNQ4 and, via regulation of calcium (Ca(2+)) entry, Ca(2+)-sensitive K(+) channels. SGK1-sensitive transporters include sodium-potassium-chloride cotransporter 2 and sodium/potassium-adenosine triphosphatase. SGK1-dependent regulation of K(+) channels and K(+) transport contributes to the stimulation of renal K(+) excretion following high K(+) intake, to insulin-induced cellular K(+) uptake and hypokalemia, to inhibition of insulin release by glucocorticoids, to stimulation of mast cell degranulation and gastric acid secretion, and to cardiac repolarization. Thus, SGK1 has a profound effect on K(+) homeostasis and on a multitude of K(+)-sensitive cellular functions.
Department of Physiology, University of Tuebingen, Gmelinstrasse 5, 72076, Tuebingen, Germany. florian.lang@uni-tuebingen.de
Florian
F
Lang
Volker
V
Vallon
D000818:Animals; D005772:Gastrointestinal Transit; D006321:Heart / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced; D017874:Immediate-Early Proteins / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D017136:Ion Transport; D007668:Kidney / Q000378:metabolism*; D051666:Kv1.5 Potassium Channel / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D007328:Insulin; D051666:Kv1.5 Potassium Channel; D011188:Potassium; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C510692:Kcnj1 protein, rat