{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T17:40:32Z","timestamp":1718646032769},"reference-count":83,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:p> Previous studies have shown that pharmacological inhibition of the phosphoinositol-3 (PI3) kinase disrupts the activation of mast cells. Through phosphoinositide-dependent kinase PDK1, PI3 kinase activates the serum- and glucocorticoid-inducible kinase 3 (SGK3). The present study explored the role of SGK3 in mast cell function. Mast cells were isolated and cultured from bone marrow (BMMCs) of gene-targeted mice lacking SGK3 ( sgk3<jats:sup> \u2212\/\u2212<\/jats:sup>) and their wild-type littermates ( sgk3<jats:sup> +\/+<\/jats:sup>). BMMC numbers in the ear conch were similar in both genotypes. Stimulation with IgE and cognate antigen triggered the release of intracellular Ca<jats:sup>2+<\/jats:sup> and entry of extracellular Ca<jats:sup>2+<\/jats:sup>. Influx of extracellular Ca<jats:sup>2+<\/jats:sup> but not Ca<jats:sup>2+<\/jats:sup> release from intracellular stores was significantly blunted in sgk3<jats:sup> \u2212\/\u2212<\/jats:sup> BMMCs compared with sgk3<jats:sup> +\/+<\/jats:sup> BMMCs. Antigen stimulation further led to a rapid increase of a K<jats:sup>+<\/jats:sup>-selective conductance in sgk3<jats:sup> +\/+<\/jats:sup> BMMCs, an effect again blunted in sgk3<jats:sup> \u2212\/\u2212<\/jats:sup> BMMCs. In contrast, the Ca<jats:sup>2+<\/jats:sup> ionophore ionomycin activated K<jats:sup>+<\/jats:sup> currents to a similar extent in sgk3<jats:sup> \u2212\/\u2212<\/jats:sup> and in sgk3<jats:sup> +\/+<\/jats:sup> BMMCs. \u03b2-Hexosaminidase release, triggered by antigen stimulation, was also significantly decreased in sgk3<jats:sup> \u2212\/\u2212<\/jats:sup> BMMCs. IgE-dependent anaphylaxis measured as a sharp decrease in body temperature upon injection of DNP-HSA antigen was again significantly blunted in sgk3<jats:sup> \u2212\/\u2212<\/jats:sup> compared with sgk3<jats:sup> +\/+<\/jats:sup> mice. Serum histamine levels measured 30 min after induction of an anaphylactic reaction were significantly lower in sgk3<jats:sup> \u2212\/\u2212<\/jats:sup> than in sgk3<jats:sup> +\/+<\/jats:sup> mice. In conclusion, both in vitro and in vivo function of BMMCs are impaired in gene targeted mice lacking SGK3. Thus SGK3 is critical for proper mast cell function. <\/jats:p>","DOI":"10.1152\/ajpcell.00539.2009","type":"journal-article","created":{"date-parts":[[2010,8,5]],"date-time":"2010-08-05T03:54:33Z","timestamp":1280980473000},"page":"C1007-C1014","source":"Crossref","is-referenced-by-count":5,"title":["Blunted IgE-mediated activation of mast cells in mice lacking the serum- and glucocorticoid-inducible kinase SGK3"],"prefix":"10.1152","volume":"299","author":[{"given":"Irina M.","family":"Zemtsova","sequence":"first","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Heise","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of T\u00fcbingen, T\u00fcbingen, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[{"name":"Department 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