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Browsing by Subject "Epithelial Sodium Channels"
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Item 60kDa Lysophospholipase, a New Sgk1 Molecular Partner Involved in the Regulation of ENaC(2010) Menniti, Miranda; Iuliano, Rodolfo; Föller, Michael; Sopjani, Mentor; Alesutan, Ioana; Mariggiò, Stefania; Nofziger, Charity; Perri, Angela M.; Amato, Rosario; Blazer-Yost, Bonnie; Corda, Daniela; Lang, Florian; Perrotti, NicolaThe serum- and glucocorticoid-regulated kinase (Sgk1) is essential for hormonal regulation of ENaC-mediated sodium transport and is involved in the transduction of growth-factor-dependent cell survival and proliferation. The identification of molecular partners for Sgk1 is crucial for the understanding of its mechanisms of action. We performed a yeast two-hybrid screening based on a human kidney cDNA library to identify molecular partners of Sgk1. As a result the screening revealed a specific interaction between Sgk1 and a 60 kDa Lysophospholipase (LysoLP). LysoLP is a poorly characterized enzyme that, based on sequence analysis, might possess lysophospholipase and asparaginase activities. We demonstrate that LysoLP has indeed a lysophospholipase activity and affects metabolic functions related to cell proliferation and regulation of membrane channels. Moreover we demonstrate in the Xenopus oocyte expression system that LysoLP downregulates basal and Sgk1-dependent ENaC activity. In conclusion LysoLP may represent a new player in the regulation of ENaC and Sgk1-dependent signaling.Item THE ROLE OF THE PHOSPHOINOSITIDE PATHWAY IN HORMONAL REGULATION OF THE EPITHELIAL SODIUM CHANNEL(2004) Blazer-Yost, Bonnie; Nofziger, CharityIn summary, insulin and aldosterone stimulate phosphatidylinositol phosphorylation, thus indicating the existence of a regulated protein at or before the PI3-kinase step. Aldosterone induces the synthesis of sgk, a downstream element of the PI pathway. Sgk is necessary, but not rate-limiting, for aldosterone- and insulin-stimulated Na+ transport. However, the enzyme appears to be rate-limiting for the natriferic action of ADH. Insulin-stimulated Na+ transport, an acute response, is dependent on PI3-kinase activity but the magnitude of the response is not altered by a cellular excess of sgk. ADH-stimulated transport is not dependent on PI3-kinase but is potentiated by an excess of sgk. The foregoing data indicate that the PI pathway is involved in several steps of the natriferic action of hormones and intersects with other pathways which regulate ENaC. Furthermore, the data are consistent with the hypothesis that activation of PI3-kinase may ultimately stimulate channel insertion as well as regulate channel endocytosis. Both of these phenomena can result in an increase of ENaC-mediated Na+ transport.