A regulated NH<sub>2</sub>-terminal Sgk1 variant with enhanced function is expressed in the collecting duct

Raikwar, Nandita S.; Liu, Kang Z.; Thomas, Christie P.

doi:10.1152/ajprenal.00191.2012

Cited by 7 publications

(13 citation statements)

References 30 publications

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“…We also reported that its encoded protein sgk1_i3 is more stable compared to sgk1 and that it stimulates apical epithelial Na + transport when expressed in FRT and in mpkCCD c14 cells (Raikwar et al. ). Sgk1 and Sgk1_i3 differ only in the NH 2 terminus where 25AA in Sgk1 is replaced by 39 AA in Sgk1_i3.…”

Section: Resultsmentioning

confidence: 92%

“…We previously showed that Sgk1_v3 is an aldosterone‐regulated transcript and that Sgk1_i3, like Sgk1, stimulates ENaC mediated Na + transport (Raikwar et al. ).…”

Section: Discussionmentioning

confidence: 99%

“…All reactions were performed using 18S as a control for RNA loading and the results quantified using the delta delta Ct method (Raikwar et al. ).…”

Section: Methodsmentioning

confidence: 99%

“…). Sgk1_v3 is expressed in a number of epithelial cells that have amiloride‐sensitive Na + transport including the DCT, CNT and CCD and this transcript is regulated by aldosterone in collecting duct epithelia in culture (Raikwar et al ). Both encoded isoforms, Sgk1_i2 and Sgk1_i3, have different NH 2 termini, are less susceptible to ubiquitination and appear to be more stable than Sgk1 protein.…”

Section: Introductionmentioning

confidence: 99%

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Aldosterone regulates a 5ʹ variant sgk1 transcript via a shared hormone response element in the sgk1 5ʹ regulatory region

Raikwar

Thomas

2017

Physiol Rep

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We previously identified a 5ʹ variant alternate transcript of Sgk1 (Sgk1_v3) encoding an NH 2‐terminal variant Sgk1 isoform, Sgk1_i3 that, like Sgk1, is expressed in the distal convoluted tubule, connecting tubule and collecting duct and can stimulate epithelial Na+ transport (Am J Physiol Renal Physiol 303: F1527–F1533, 2012). We now demonstrate that, similar to Sgk1, aldosterone and glucocorticoids stimulate Sgk1_v3 expression in cell lines from the collecting duct and airway epithelia. In mice, short term aldosterone infusion and maneuvers that increase endogenous aldosterone secretion including dietary Na+ deprivation and K+ loading increases distal nephron Sgk1_v3 expression in vivo. Although Sgk1_v3 has a different 5ʹ proximal regulatory region from Sgk1, the transcription start sites are less than 1000 bp apart. We cloned the 5ʹ regulatory region for Sgk1 and Sgk_v3 upstream of a luciferase gene and by deletion and reporter gene analysis we localized the corticosteroid regulatory region for Sgk1_v3 to a glucocorticoid response element (GRE) that had previously been identified for Sgk1 (Am J Physiol Endo Metab 283: E971–E979, 2002). We tested this element with MR in an MR‐null cell line and demonstrate that aldosterone stimulates Sgk1 and Sgk1_v3 via this GRE. We conclude that corticosteroids stimulate Sgk1 and Sgk1_v3 expression in epithelial cells via activation of a common conserved GRE in the 5ʹ flanking region of Sgk1.

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Section: Resultsmentioning

confidence: 92%

“…We previously showed that Sgk1_v3 is an aldosterone‐regulated transcript and that Sgk1_i3, like Sgk1, stimulates ENaC mediated Na + transport (Raikwar et al. ).…”

Section: Discussionmentioning

confidence: 99%

“…All reactions were performed using 18S as a control for RNA loading and the results quantified using the delta delta Ct method (Raikwar et al. ).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Aldosterone regulates a 5ʹ variant sgk1 transcript via a shared hormone response element in the sgk1 5ʹ regulatory region

Raikwar

Thomas

2017

Physiol Rep

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“…SGK1 has also been shown to enhance cell-surface expression of SLC6A19 in Xenopus oocytes [25]. Since SGK1 has five isoforms (SGK1a-e) [28][29][30], a primer pair from the conserved region of these isoforms was chosen so that the total mRNA level was measured by qRT-PCR.…”

Section: Reduced Sgk1 Mrna Expression In Tis7mentioning

confidence: 99%

Proline Absorption and SGK1 Expression are Inhibited in Intestinal Tis7 Transgenic Mice

Lü¹,

Garcia²,

Geisman³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Expression of the transcriptional co-regulator tis7 is markedly increased in the adaptive small intestine in a mouse model of short bowel syndrome. Transgenic mice with enterocytic overexpression of tis7 (tis7 tg ) have accelerated triglyceride absorption, with increased adiposity yet reduced skeletal muscle mass. To further explore this phenotype, we examined whether tis7 also regulates amino acid and carbohydrate absorption. Methods: Small intestinal glucose and amino acid uptake were quantified in wild type (WT) and tis7 tg mice. Amino acid transporter expression was assessed by qRT-PCR and immunoblot. Apical cell surface transporter expression was quantified by cell surface biotinylation. Results: Active glucose uptake rates were unchanged. Uptake of proline but not leucine was significantly reduced in tis7 tg vs. WT jejunum. Expression of serum and glucocorticoid-induced kinase 1 (SGK1), a solute carrier activator, was inhibited in tis7 tg jejunum. Apical membrane expression of the proline transporter SLC6A20 was reduced in tis7 tg jejunum. Conclusions: Tis7 overexpression in enterocytes inhibits proline uptake, associated with decreased expression of activated SGK1 and reduced cell surface expression of SLC6A20. Consistent with the observed tis7 tg phenotype, tis7 overexpression increases triglyceride absorption but has adverse effects on the uptake of selected amino acids. Tis7 has pleiotropic effects on nutrient absorption.

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A G-quadruplex nanoswitch in the SGK1 promoter regulates isoform expression by K+/Na+ balance and resveratrol binding

Chen

et al. 2021

Biochimica et Biophysica Acta (BBA) - General Subjects

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A regulated NH₂-terminal Sgk1 variant with enhanced function is expressed in the collecting duct

Abstract: Raikwar NS, Liu KZ, Thomas CP. A regulated NH2-terminal Sgk1 variant with enhanced function is expressed in the collecting duct.

Cited by 7 publications

References 30 publications

Aldosterone regulates a 5ʹ variant sgk1 transcript via a shared hormone response element in the sgk1 5ʹ regulatory region

Aldosterone regulates a 5ʹ variant sgk1 transcript via a shared hormone response element in the sgk1 5ʹ regulatory region

Proline Absorption and SGK1 Expression are Inhibited in Intestinal Tis7 Transgenic Mice

A G-quadruplex nanoswitch in the SGK1 promoter regulates isoform expression by K+/Na+ balance and resveratrol binding

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