Regulation of sgk by aldosterone and its effects on the epithelial Na(+) channel.
Aldosterone is the major corticosteroid regulating Na(+) absorption in tight epithelia and acts primarily by activating the epithelial Na(+) channel (ENaC) through unknown induced proteins. Recently, it has been reported that aldosterone induces the serum- and glucocorticoid-dependent kinase sgk and that coexpressing ENaC with this kinase in Xenopus laevis oocytes increases the amiloride-sensitive Na(+) current (Chen SY, Bhargava A, Mastroberardino L, Meijer OC, Wang J, Buse P, Firestone GL, Verrey F, and Pearce D. Proc Natl Acad Sci USA 96: 2514-2519, 1999). The present study was done to further characterize regulation of sgk by aldosterone in native mammalian epithelia and to examine its effect on ENaC. With both in vivo and in vitro protocols, an almost fivefold increase in the abundance of sgk mRNA has been demonstrated in rat kidney and colon but not in lung. Induction of sgk by aldosterone was detected in kidney cortex and medulla, whereas the papilla expressed a constitutively high level of the kinase. The increase in sgk mRNA was detected as early as 30 min after the hormonal application and was independent of de novo protein synthesis. The observed aldosterone dose-response relationships suggest that the response is mediated, at least in part, by occupancy of the mineralocorticoid receptor. Coexpressing sgk and ENaC in Xenopus oocytes evoked a fourfold increase in the amiloride-blockable Na(+) channel activity. A point mutation in the beta-subunit known to impair regulation of the channel by Nedd4 (Y618A) had no significant effect on the response to sgk.
Shigaev
A
A
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Asher
C
C
Latter
H
H
Garty
H
H
Reuveny
E
E
D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D007668:Kidney / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins; D009865:Oocytes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D015222:Sodium Channels; D000099184:Serum-Glucocorticoid Regulated Kinases