Role of SGK in mineralocorticoid-regulated sodium transport.
Mineralocorticoids stimulate electrogenic Na+ transport in tight epithelia by altering the transcription of specific genes. Although the earliest mineralocorticoid effect is to increase the activity of the epithelial sodium channel (ENaC), ENaC mRNA and protein levels do not change. Instead, physiologic observations suggest that a mineralocorticoid target gene(s) encodes an ENaC regulator(s). To begin to identify and characterize mineralocorticoid-regulated target genes, we used suppression-subtractive hybridization to generate a cDNA library from A6 cells, a stable cell line of Xenopus laevis of distal nephron origin. A serine-threonine kinase, SGK, was identified from this screen. Sequence comparison revealed that frog, rat, and human SGK are 92% identical and 96% similar at the amino acid level. SGK mRNA was confirmed by Northern blot to be strongly and rapidly corticosteroid stimulated in A6 cells. In situ hybridization revealed that SGK was strongly stimulated by aldosterone in rat collecting duct but not proximal tubule cells. Low levels of SGK were present in rat glomeruli, but SGK was unregulated in this structure. Finally, SGK stimulated ENaC activity approximately sevenfold when coexpressed in Xenopus laevis oocytes. These data suggest that SGK is an important mediator of aldosterone effects on Na+ transport in tight epithelia. In view of the existence of SGK homologues in invertebrates, it is interesting to speculate that SGK is an ancient kinase that was adapted to the control of epithelial Na+ transport by early vertebrates as they made the transition from a marine to a freshwater environment.
Pearce
D
D
Department of Medicine, and Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA. pearced@medicine.ucsf.edu
Verrey
F
F
Chen
S Y
SY
Mastroberardino
L
L
Meijer
O C
OC
Wang
J
J
Bhargava
A
A
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins; D008901:Mineralocorticoids / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D008901:Mineralocorticoids; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D012964:Sodium; D000099184:Serum-Glucocorticoid Regulated Kinases