{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T19:44:02Z","timestamp":1774122242976,"version":"3.50.1"},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":3590,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/2.5\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,10,15]]},"abstract":"<jats:p>The role of SGK1 (serum- and glucocorticoid-induced protein kinase 1) in the glucocorticoid induction of \u03b1-ENaC (epithelial Na+ channel \u03b1 subunit) gene transcription was explored by monitoring the transcriptional activity of a luciferase-linked, \u03b1-ENaC reporter gene construct (pGL3-KR1) expressed in H441 airway epithelial cells. Dexamethasone evoked a concentration-dependent (EC50\u223c4 \u03bcM) increase in transcriptional activity dependent upon a glucocorticoid response element in the \u03b1-ENaC sequence. Although dexamethasone also activated endogenous SGK1, artificially increasing cellular SGK1 activity by expressing a constitutively active SGK1 mutant (SGK1-S422D) in hormone-deprived cells did not activate pGL3-KR1. Moreover, expression of catalytically inactive SGK1 (SGK1-K127A) suppressed the activation of endogenous SGK1 without affecting the transcriptional response to dexamethasone. Increasing cellular PI3K (phosphoinositide 3-kinase) activity by expressing a membrane-anchored form of the catalytic PI3K-P110\u03b1 subunit [CD2 (cluster of differentiation 2)-P110\u03b1] also activated endogenous SGK1 without affecting pGL3-KR1activity. A catalytically inactive form of CD2-P110\u03b1 (R1130P), on the other hand, prevented the dexamethasone-induced activation of SGK1, but did not inhibit the activation of pGL3-KR1. However, expression of SGK1-S422D or CD2-P110\u03b1 enhanced the transcriptional responses to maximally effective concentrations of dexamethasone and this effect occurred with no change in EC50. Dexamethasone-induced (0.3\u2013300\u00a0nM) activation of pGL3-KR1 was unaffected by inhibitors of PI3K (PI-103 and wortmanin) and by rapamycin, a selective inhibitor of the TORC1 (target of rapamycin complex 1) signalling complex. Dexamethasone-induced activation of the \u03b1-ENaC gene promoter can thus occur independently of SGK1\/PI3K, although this pathway does provide a mechanism that allows this transcriptional response to dexamethasone to be enhanced.<\/jats:p>","DOI":"10.1042\/bj20090366","type":"journal-article","created":{"date-parts":[[2009,7,22]],"date-time":"2009-07-22T09:04:13Z","timestamp":1248253453000},"page":"189-197","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Glucocorticoids can activate the \u03b1-ENaC gene promoter independently of SGK1"],"prefix":"10.1042","volume":"423","author":[{"given":"Niall","family":"McTavish","sequence":"first","affiliation":[{"name":"Centre for Cardiovascular and Pulmonary Research, Division of Medical Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennet","family":"Getty","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Pulmonary Research, Division of Medical Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Burchell","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Pulmonary Research, Division of Medical Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart\u00a0M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular and Pulmonary Research, Division of Medical Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2009,9,25]]},"reference":[{"key":"2021112215164073700_B1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1203\/00006450-199006000-00010","article-title":"Synergistic action of triiodothyronine and hydrocortisone on epinephrine-induced reabsorption of fetal lung liquid","volume":"27","author":"Barker","year":"1990","journal-title":"Pediat. 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