h-sgk serine-threonine protein kinase gene as transcriptional target of transforming growth factor β in human intestine

Waldegger, Siegfried; Klingel, Karin; Barth, Petra; Sauter, Martina; Lanzendörfer, Martina; Kandolf, Reinhard; Läng, Florian

doi:10.1016/s0016-5085(99)70011-9

Cited by 134 publications

(129 citation statements)

References 47 publications

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“…It participates in the regulation of intestinal transport (38), peripheral glucose uptake (39), and insulin release from pancreatic ␤-cells (40). Several observations point to its pivotal role in fibrosing disease (41)(42)(43)(44)(45). Nothing is known, however, about the influence of SGK1 on those ion channels, which are decisive in the regulation of mast cell function.…”

Section: Impaired Mast Cell Activation In Gene-targeted Mice Lacking mentioning

confidence: 99%

Impaired Mast Cell Activation in Gene-Targeted Mice Lacking the Serum- and Glucocorticoid-Inducible Kinase SGK1

Sobiesiak

Shumilina

Lam

et al. 2009

The Journal of Immunology

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The PI3K pathway plays a pivotal role in the stimulation of mast cells. PI3K-dependent kinases include the serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored the role of SGK1 in mast cell function. Mast cells were isolated from bone marrow (BMMC) of SGK1 knockout mice (sgk1−/−) and their wild-type littermates (sgk1+/+). The BMMC number as well as CD117, CD34, and FcεRI expression in BMCCs were similar in both genotypes. Upon Ag stimulation of the FcεRI receptor, Ca2+ entry but not Ca2+ release from intracellular stores was markedly impaired in sgk1−/− BMMCs. The currents through Ca2+-activated K+ channels induced by Ag were significantly higher in sgk1+/+ BMMCs than in sgk1−/− BMMCs. Treatment with the Ca2+ ionophore ionomycin (1 μM) led to activation of the K+ channels in both genotypes, indicating that the Ca2+-activated K+ channels are similarly expressed and sensitive to activation by Ca2+ in sgk1+/+ and sgk1−/− BMMCs, and that blunted stimulation of Ca2+-activated K+ channels was secondary to decreased Ca2+ entry. Ag-IgE-induced degranulation and early IL-6 secretion were also significantly blunted in sgk1−/− BMMCs. The decrease in body temperature following Ag treatment, which reflects an anaphylactic reaction, was substantially reduced in sgk1−/− mice, pointing to impaired mast cell function in vivo. Serum histamine levels measured 30 min after induction of an anaphylactic reaction were significantly lower in sgk1−/− than in sgk1+/+mice. The observations reveal a critical role for SGK1 in ion channel regulation and the function of mast cells, and thus disclose a completely novel player in the regulation of allergic reaction.

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Section: Impaired Mast Cell Activation In Gene-targeted Mice Lacking mentioning

confidence: 99%

Impaired Mast Cell Activation in Gene-Targeted Mice Lacking the Serum- and Glucocorticoid-Inducible Kinase SGK1

Sobiesiak

Shumilina

Lam

et al. 2009

The Journal of Immunology

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“…Although SGK isoforms show a high homology, only SGK1 is activated by dexamethasone and serum (19). Based on its regulation by glucocorticoids and its expression in intestinal villi and renal proximal tubules (19,31), only SGK1 was pursued for further studies, and SGK3 was excluded from further analyses despite its interaction with NHERF2.…”

Section: Nherf2 Is Necessary For the Activation Of Nhe3mentioning

confidence: 99%

Glucocorticoid Activation of Na+/H+Exchanger Isoform 3 Revisited

Yun

Chen

Läng

2002

Journal of Biological Chemistry

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168

211

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The stimulative effect of glucocorticoids on intestinal salt and water absorption has been known for more than two decades. However, molecular mechanisms underlying this activation remain elusive. Previous studies showed that methylprednisolone specifically increased Na ؉ /H ؉ exchanger isoform (NHE) 3 mRNA in ileum and kidney without affecting NHE1 mRNA levels. These results suggest that glucocorticoids activate NHE3 activity by induction of NHE3 transcripts. We recently found in PS120 and opossum kidney cells that chronic incubation with dexamethasone activated NHE3 independent of gene induction, indicating that the transcriptional activation may not be the only determining factor in the NHE3 activation. Furthermore, dexamethasone activated NHE3 activity only in the presence of a NHE3 regulatory protein, NHERF2, which was previously shown to confer cAMP-dependent inhibition of NHE3. This activation of NHE3 could not be duplicated by NHERF1. We identified serum-and glucocorticoid-induced protein kinase, SGK1, as the protein interacting with PDZ domains of NHERF2 to regulate NHE3 activity. The expression of SGK1 enhanced NHE3 transport in PS120 fibroblasts. In addition, the "kinase-dead" SGK1 blocked activation of NHE3 by dexamethasone in opossum kidney cells. These data demonstrated that glucocorticoid activation of NHE3 requires the activation of SGK1 and the presence of NHERF2 acting as a scaffold protein.

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“…Moreover, the physiological stress hormones, glucocorticoids, stimulate sgk promoter activity through a glucocorticoid response element, and sgk is a transcriptional target of the p53 tumor suppressor gene, a known target of genotoxic stress (28,32). Consistent with a role for Sgk in the cellular stress response, sgk transcripts have been shown to be elevated in response to ischemic injury of the brain, changes in cell volume, and inflammatory disease and in a screen for transcripts involved in wound repair in fibroblasts (33)(34)(35)(36). Therefore, to determine whether transcription of the sgk gene is a component of the stress response in mammalian cells, the hyperosmolar regulation of Sgk was examined in mammary epithelial cells.…”

mentioning

confidence: 93%

Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway

Bell¹,

Leong²,

Kim³

et al. 2000

Journal of Biological Chemistry

143

149

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We have established that the serum-and glucocorticoid-inducible protein kinase (Sgk) is a new component of the hyperosmotic stress response. Treatment of NMuMg mammary epithelial cells with the organic osmolyte, sorbitol, caused the stable accumulation of Sgk transcripts and protein after an approximately 4-h lag. Transient transfection of a series of sgk-CAT reporter plasmids containing either 5 deletions or continuous 6-base pair substitutions identified a hyperosmotic stress-regulated element that is GC-rich and is necessary for the sorbitol stimulation of sgk gene promoter activity. Gel shift analysis identified four major DNAprotein complexes in the hyperosmotic stress-regulated element that, by competition with excess consensus wild type and mutant oligonucleotides and by antibody supershifts, contains the Sp1 transcription factor. Several lines of evidence suggest that the p38 MAPK signaling pathway mediates the hyperosmotic stress stimulation of sgk gene expression. Treatment with pharmacological inhibitors of p38 MAPK or with a dominant negative form of MKK3, an upstream regulator of p38 MAPK, significantly reduced or ablated the sorbitol induction of sgk promoter activity or protein production. Using an in vitro peptide transphosphorylation assay, sorbitol treatment activates either endogenous or exogenous Sgk that is localized to the cytoplasmic compartment. Thus, we propose that the stimulated expression of enzymatically active Sgk after sorbitol treatment is a newly defined component of the p38 MAPK-mediated response to hyperosmotic stress.

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h-sgk serine-threonine protein kinase gene as transcriptional target of transforming growth factor β in human intestine

Cited by 134 publications

References 47 publications

Impaired Mast Cell Activation in Gene-Targeted Mice Lacking the Serum- and Glucocorticoid-Inducible Kinase SGK1

Impaired Mast Cell Activation in Gene-Targeted Mice Lacking the Serum- and Glucocorticoid-Inducible Kinase SGK1

Glucocorticoid Activation of Na+/H+Exchanger Isoform 3 Revisited

Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway

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