Abstract
Activation of epithelial sodium channels (ENaC) by aldosterone, insulin, or insulin-like growth factor-1 (IGF-1) in renal epithelial cells (including the Xenopus laevis renal cell line A6) appears to share some common signaling elements subsequent to the initial insulin or IGF-1 receptor activation. Previously, the convergence point for insulin or IGF-1 and aldosterone signaling was assumed to be downstream of the receptor at the level of phosphatidylinositol 3-kinase (PI3-K); however, this study shows aldosterone directly transactivates the IGF-1 receptor (IGF-1R). In A6 cells, 10-min exposure to aldosterone increased the phosphorylation of the IGF-1 receptor, insulin receptor substrate-1 (IRS-1), and Akt (PKB). Furthermore, aldosterone activated PI3-K and phosphorylation of the most downstream element, Akt, was blocked by the specific PI3-K inhibitor LY-294002. Transactivation requires aldosterone binding to the mineralocorticoid/glucocorticoid receptor and does not require transcription.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Aldosterone / physiology*
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Animals
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Cell Line
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Dactinomycin / pharmacology
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Epithelial Cells
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Insulin / pharmacology
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Insulin Receptor Substrate Proteins
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Insulin-Like Growth Factor I / pharmacology
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Kidney / cytology
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Mifepristone / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoproteins
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Phosphorylation
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor, IGF Type 1 / physiology*
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Receptor, Insulin / physiology
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Receptors, Glucocorticoid / physiology
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Receptors, Mineralocorticoid / physiology
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Signal Transduction / drug effects
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Spironolactone / pharmacology
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Transcriptional Activation / drug effects*
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Xenopus Proteins
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Xenopus laevis
Substances
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Insulin
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Insulin Receptor Substrate Proteins
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Phosphoproteins
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Receptors, Glucocorticoid
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Receptors, Mineralocorticoid
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Xenopus Proteins
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irs1 protein, Xenopus
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Dactinomycin
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Spironolactone
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Mifepristone
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Aldosterone
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Insulin-Like Growth Factor I
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Phosphatidylinositol 3-Kinases
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Receptor, IGF Type 1
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Receptor, Insulin
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Proto-Oncogene Proteins c-akt