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We evaluated the early intermediate pathways involved in the up\u2010regulation of SGK1 by DbcAMP and whether SGK1 is a prerequisite for induction of \u03b1\u2010ENaC expression. Submandibular gland epithelial (SMG\u2010C6) cells treated with DbcAMP (1 mM) induced both SGK1 mRNA and protein expression. DbcAMP\u2010stimulated SGK1 mRNA expression was decreased by actinomycin D and mRNA and protein expressions were attenuated by PKA inhibitors (H\u201089 and KT5720). Inhibition of PI3\u2010K with either LY294002 or dominant negative PI3\u2010K reduced DbcAMP\u2010stimulated SGK1 protein and mRNA levels, attenuated the phosphorylation of CREB (a cAMP\u2010activated transcription factor) and decreased \u03b1\u2010ENaC protein levels and Na<jats:sup>+<\/jats:sup> transport. In addition, the combination of PKA inhibitors with dominant negative PI3\u2010K synergistically inhibited DbcAMP\u2010induced Na<jats:sup>+<\/jats:sup> transport. Inhibition of SGK1 expression by siRNA decreased but did not obliterate DbcAMP\u2010induced \u03b1\u2010ENaC expression. Thus, in a cell line which endogenously exhibits minimal \u03b1\u2010ENaC expression, induction of SGK1 by DbcAMP occurs via the PI3\u2010K and PKA pathways. Increased \u03b1\u2010ENaC levels and function are partly dependent upon the early induction of SGK1 expression. J. Cell. Physiol. 217: 632\u2013642, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21534","type":"journal-article","created":{"date-parts":[[2008,7,9]],"date-time":"2008-07-09T15:05:04Z","timestamp":1215615904000},"page":"632-642","source":"Crossref","is-referenced-by-count":22,"title":["Induction of serum\u2010 and glucocorticoid\u2010induced kinase\u20101 (SGK1) by cAMP regulates increases in \u03b1\u2010ENaC"],"prefix":"10.1002","volume":"217","author":[{"given":"Margarita M.","family":"Vasquez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R.","family":"Seidner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara 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