Induction of serum- and glucocorticoid-induced kinase-1 (SGK1) by cAMP regulates increases in α-ENaC

Margarita M. Vasquez, Robert Castro, Steven R. Seidner, Barbara M. Henson, Daniel J. Ashton, Shamimunisa B. Mustafa

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

α-ENaC expression and activity is regulated by a variety of hormones including β-adrenergic agonists via the second messenger cAMP. We evaluated the early intermediate pathways involved in the up-regulation of SGK1 by DbcAMP and whether SGK1 is a prerequisite for induction of α-ENaC expression. Submandibular gland epithelial (SMG-C6) cells treated with DbcAMP (1 mM) induced both SGK1 mRNA and protein expression. DbcAMP-stimulated SGK1 mRNA expression was decreased by actinomycin D and mRNA and protein expressions were attenuated by PKA inhibitors (H-89 and KT5720). Inhibition of PI3-K with either LY294002 or dominant negative PI3-K reduced DbcAMP-stimulated SGK1 protein and mRNA levels, attenuated the phosphorylation of CREB (a cAMP-activated transcription factor) and decreased α-ENaC protein levels and Na+ transport. In addition, the combination of PKA inhibitors with dominant negative PI3-K synergistically inhibited DbcAMP-induced Na+ transport. Inhibition of SGK1 expression by siRNA decreased but did not obliterate DbcAMP-induced α-ENaC expression. Thus, in a cell line which endogenously exhibits minimal α-ENaC expression, induction of SGK1 by DbcAMP occurs via the PI3-K and PKA pathways. Increased α-ENaC levels and function are partly dependent upon the early induction of SGK1 expression.

Original languageEnglish (US)
Pages (from-to)632-642
Number of pages11
JournalJournal of Cellular Physiology
Volume217
Issue number3
DOIs
StatePublished - Dec 1 2008

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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