{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:28:02Z","timestamp":1791217682539,"version":"4.1.0"},"reference-count":44,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2001,2,1]]},"abstract":"<jats:p>The epithelial Na<jats:sup>+<\/jats:sup>channel (ENaC) constitutes the rate-limiting step for Na<jats:sup>+<\/jats:sup>transport across tight epithelia and is the principal target of hormonal regulation, particularly by insulin and mineralocorticoids. Recently, the serine-threonine kinase (SGK) was identified as a rapidly mineralocorticoid-responsive gene, the product of which stimulates ENaC-mediated Na<jats:sup>+<\/jats:sup>transport. Like its close relative, protein kinase B (also called Akt), SGK's kinase activity is dependent on phosphatidylinositol 3-kinase (PI3K), a key mediator of insulin signaling. In our study we show that PI3K is required for SGK-dependent stimulation of ENaC-mediated Na<jats:sup>+<\/jats:sup>transport as well as for the production of the phosphorylated form of SGK. In A6 kidney cells, mineralocorticoid induction of the phosphorylated form of SGK preceded the increase in Na<jats:sup>+<\/jats:sup>transport, and specific inhibition of PI3K inhibited both phosphorylation of SGK and mineralocorticoid-induced Na<jats:sup>+<\/jats:sup>transport. Insulin both augmented SGK phosphorylation and synergized with mineralocorticoids in stimulating Na<jats:sup>+<\/jats:sup>transport. In a Xenopus laevisoocyte coexpression assay, SGK-stimulated ENaC activity was also markedly reduced by PI3K inhibition. Finally, in vitro-translated SGK specifically interacted with the ENaC subunits expressed in Escherichia coli as glutathione S-transferase fusion proteins. These data suggest that SGK is a PI3K-dependent integrator of insulin and mineralocorticoid actions that interacts with ENaC subunits to control Na<jats:sup>+<\/jats:sup>entry into kidney collecting duct cells.<\/jats:p>","DOI":"10.1152\/ajprenal.2001.280.2.f303","type":"journal-article","created":{"date-parts":[[2017,12,23]],"date-time":"2017-12-23T13:20:15Z","timestamp":1514035215000},"page":"F303-F313","source":"Crossref","is-referenced-by-count":159,"title":["SGK integrates insulin and mineralocorticoid regulation of epithelial sodium transport"],"prefix":"10.1152","volume":"280","author":[{"given":"Jian","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco 94143; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Barbry","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco 94143; 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