Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ

Bhalla, Vivek; Soundararajan, Rama; Pao, Alan C.; Li, Hongyan; Pearce, David

doi:10.1152/ajprenal.00061.2006

Cited by 94 publications

(73 citation statements)

References 89 publications

(104 reference statements)

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“…RNA interference experiments also supported a role for GILZ in the inhibition of CXCL8 expression in endothelial cells (Eddleston et al, 2007). On the other hand, GILZ stimulated rather than suppressed the expression and activity of the epithelial sodium channel α (ENaCα) (Bhalla et al, 2006;Soundararajan et al, 2005), possibly via inhibition of the ERK pathway (Ayroldi et al, 2002;Soundararajan et al, 2005). ENaCα expression is thought to contribute to GC-induced hypertension (Fuller et al, 2000;Itani et al, 2002;Sayegh et al, 1999;Stokes and Sigmund, 1998).…”

Section: A Clarkmentioning

confidence: 89%

“…GCs upregulate glucocorticoid inducible leucine zipper (GILZ) expression in T cells (Asselin-Labat et al, 2004;D'Adamio et al, 1997;Mittelstadt and Ashwell, 2001;Riccardi et al, 2001), mast cells , eosinophils (Arthaningtyas et al, 2005), epithelial (Bhalla et al, 2006;Chivers et al, 2006;Eddleston et al, 2007;Soundararajan et al, 2005;Wang et al, 2004), and myeloid cells (Berrebi et al, 2003;Cohen et al, 2006;Ehrchen et al, 2007). Relatively high basal GILZ expression has also been recorded in brain, lung and skeletal muscle .…”

Section: Glucocorticoid Inducible Leucine Zippermentioning

confidence: 99%

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Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

237

193

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Section: A Clarkmentioning

confidence: 89%

Section: Glucocorticoid Inducible Leucine Zippermentioning

confidence: 99%

Anti-inflammatory functions of glucocorticoid-induced genes

Clark

2007

Molecular and Cellular Endocrinology

237

193

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“…There have been hints that the PI3K and Raf-MEK-ERK pathways intersect in the control of ENaC (12,13). Although SGK1 and GILZ1 have been shown to disinhibit each inhibitory pathway separately (13), recent observations reveal that ENaC phosphorylated by activated ERK exhibits enhanced interaction with Nedd4-1 and subsequent internalization and degradation (14).…”

mentioning

confidence: 99%

“…Although SGK1 and GILZ1 have been shown to disinhibit each inhibitory pathway separately (13), recent observations reveal that ENaC phosphorylated by activated ERK exhibits enhanced interaction with Nedd4-1 and subsequent internalization and degradation (14). Nedd4-1 is a close relative of Nedd4-2 with WW domains that bind ENaC similarly (14).…”

mentioning

confidence: 99%

Epithelial sodium channel regulated by differential composition of a signaling complex

Soundararajan¹,

Melters²,

Shih³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Hormonal control of transepithelial sodium (Na ؉ ) transport utilizes phosphatidylinositide 3 -kinase (PI3K) and Raf-MAPK/ERK kinase (MEK)-ERK-dependent signaling pathways, which impact numerous cell functions. How signals transmitted by these pathways are sorted and appropriately transmitted to alter Na ؉ transport without altering other physiologic processes is not well understood. Here, we report the identification of a signaling complex that selectively modulates the cell surface expression of the epithelial sodium channel (ENaC), an ion channel that is essential for fluid and electrolyte balance in mammals. Raf-1 and the ubiquitin ligase, Nedd4-2, are constitutively-expressed inhibitory components of this ENaC regulatory complex, which interact with, and decrease the expression of, cell surface ENaC. The activities of Nedd4-2 and Raf-1 are inhibited cooperatively by the PI3K-dependent kinase serum-and glucocorticoid-induced kinase 1 (SGK1), and the Raf-1-interacting protein glucocorticoid-induced leucine zipper (GILZ1), which are aldosterone-stimulated components of the complex. Together, SGK1 and GILZ1 synergistically stimulate ENaC cell surface expression. Interestingly, GILZ1 and SGK1 do not have synergistic, and in fact have opposite, effects on an unrelated activity, FKHRL1-driven gene transcription. Together, these data suggest that GILZ1 and SGK1 provide a physical and functional link between the PI3K-and Raf-1-dependent signaling modules and represent a unique mechanism for specifically controlling Na ؉ transport without inappropriately activating other cell functions.glucocorticoid-induced leucine zipper protein ͉ Nedd4-2 ͉ Raf-1 ͉ serum-and glucocorticoid-induced kinase 1

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“…It is a member of the TSC22D (transforming growth factor ␤1-stimulated clone 22 domain) family of proteins that are widely expressed and appear to impact multiple biological processes (2)(3)(4)(5). TSC22D1 (or, simply, TSC22) was first isolated based on its rapid and transient transcriptional induction by transforming growth factor ␤1 (6).…”

mentioning

confidence: 99%

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

Soundararajan

Wang

Melters

et al. 2007

Journal of Biological Chemistry

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Glucocorticoid-induced leucine zipper protein (GILZ) is expressed in both epithelial and immune tissues and modulates a variety of cellular functions, including proliferation and epithelial sodium channel (ENaC) activity. A number of reports have described various GILZ activities, focusing on a single isoform with molecular mass of ϳ17 kDa, now termed GILZ1. In GILZ immunoblots using a newly developed antiserum, we detected multiple species in extracts from cultured kidney cells. Mass spectrometric analysis revealed that one of these represented a previously uncharacterized distinct isoform of GILZ, GILZ2. Rapid amplification of cDNA ends was used to clone cDNAs corresponding to four isoforms, which, in addition to GILZ1 and GILZ2, included new isoforms GILZ3 and GILZ4. Heterologous expression of these four GILZ isoforms in cultured cells revealed striking functional differences. Notably, GILZ1 was the only isoform that significantly stimulated ENaCmediated Na ؉ current in a kidney collecting duct cell line, although GILZ2 and GILZ3 also stimulated ENaC surface expression in HEK 293 cells. GILZ1 and GILZ3, and to a lesser extent GILZ2, inhibited ERK phosphorylation. Interestingly, GILZ4, which had no effect on either ENaC or ERK, potently suppressed cellular proliferation, as did GILZ1, but not GILZ2 or GILZ3. Finally, rat and mouse tissues all expressed multiple GILZ species but varied in the relative abundance of each. These data suggest that multiple GILZ isoforms are expressed in most cells and tissues and that these play distinct roles in regulating key cellular functions, including proliferation and ion transport. Furthermore, GILZ inhibition of ERK appears to play an essential role in stimulation of cell surface ENaC but not in inhibition of proliferation. Glucocorticoid-induced leucine zipper (GILZ)3 is a small leucine zipper protein of ϳ17 kDa. As its name implies, GILZ was first discovered as a dexamethasone-induced transcript in murine thymocytes, which it protects from apoptosis induced by treatment with anti-CD3 antibody (1). It is a member of the TSC22D (transforming growth factor ␤1-stimulated clone 22 domain) family of proteins that are widely expressed and appear to impact multiple biological processes (2-5). TSC22D1 (or, simply, TSC22) was first isolated based on its rapid and transient transcriptional induction by transforming growth factor ␤1 (6). It is a potential tumor suppressor gene and has been shown to down-regulate cell proliferation and induce apoptosis in human salivary gland (7,8). Its expression in human fetal tissues (9) and, more recently, its detection at sites of epithelial-mesenchymal interactions during mouse embryogenesis (10) suggest an important role for this protein during vertebrate development. A similar role has been identified for the TSC22 homologue, bunched, in developing Drosophila larvae (11). TSC22D2 and TSC22D4 are expressed in renal cortex, medulla, and papilla and are involved in adaptation of these cells to hypertonicity (4). These two transcripts are signifi...

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Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ

Cited by 94 publications

References 89 publications

Anti-inflammatory functions of glucocorticoid-induced genes

Anti-inflammatory functions of glucocorticoid-induced genes

Epithelial sodium channel regulated by differential composition of a signaling complex

Differential Activities of Glucocorticoid-induced Leucine Zipper Protein Isoforms

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