Abstract
The purpose of this study was to examine the role of the serum- and glucocorticoid-induced kinase (SGK) in the activation of the epithelial sodium channel (ENaC) by aldosterone, arginine vasopressin (AVP), and insulin. We used a tetracycline-inducible system to control the expression of wild-type (SGK(wt)(T)), constitutively active (S425D mutation; SGK(S425D)(T)), or inactive (K130M mutation; SGK(K130M)(T)) SGK in A6 cells independently of hormonal stimulation. The effect of SGK expression on ENaC activity was monitored by measuring transepithelial amiloride-sensitive short-circuit current (I(sc)) of transfected A6 cell lines. Expression of SGK(wt)(T) or SGK(S425D)(T) and aldosterone stimulation have additive effects on I(sc). Although SGK could play some role in the aldosterone response, our results suggest that other mechanisms take place. SGK(S425D)(T) abrogates the responses to AVP and insulin; hence, in the signaling pathways of these hormones there is a shared step that is stimulated by SGK. Because AVP and insulin induce fusion of vesicles to the apical membrane, our results support the notion that SGK promotes incorporation of channels in the apical membrane.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aldosterone / metabolism*
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Aldosterone / pharmacology
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Animals
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Arginine Vasopressin / metabolism*
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Arginine Vasopressin / pharmacology
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Carrier Proteins / drug effects
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Carrier Proteins / metabolism
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cells, Cultured
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Clone Cells / drug effects
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Clone Cells / metabolism
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DNA, Complementary / drug effects
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DNA, Complementary / genetics
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DNA, Complementary / metabolism
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism*
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Epithelial Sodium Channels
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Enzymologic / physiology
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Immediate-Early Proteins
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Insulin / metabolism*
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Insulin / pharmacology
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Mutation / drug effects
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Mutation / physiology
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Nephrons / cytology
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Nephrons / metabolism*
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Nuclear Proteins*
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Phosphatidylinositol 3-Kinases / drug effects
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Serine-Threonine Kinases / drug effects
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Repressor Proteins / drug effects
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Sodium / metabolism
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Sodium Channels / drug effects
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Sodium Channels / genetics
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Sodium Channels / metabolism*
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Tetracycline / pharmacology
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Xenopus laevis
Substances
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Carrier Proteins
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DNA, Complementary
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Epithelial Sodium Channels
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Immediate-Early Proteins
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Insulin
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Nuclear Proteins
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Repressor Proteins
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Sodium Channels
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Arginine Vasopressin
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Aldosterone
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Sodium
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Protein Serine-Threonine Kinases
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serum-glucocorticoid regulated kinase
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Tetracycline