Disease relevance of Sgk

• These results provide an insight into the alterations of sgk-1 gene expression in the rat hippocampus after transient global cerebral ischemia [1].
• Expression of the serum/glucocorticoid regulated kinase-1 (sgk-1) gene has been reported to be induced by various stress stimuli such as hyper- or hypo-osmotic stress, UV irradiation, and heat shock stress; however, its association with global ischemia in the brain has not been studied [1].
• In addition, proteinuria, podocyte damage, and Sgk1 upregulation were significantly alleviated by tempol, a membrane-permeable superoxide dismutase, suggesting the pathogenic role of oxidative stress [2].
• Aldosterone-induced upregulation of NCC, Sgk1, and ENaC likely contributes to the antinatriuretic phase of metabolic acidosis [3].

High impact information on Sgk

• Consistent with an active mechanism of nuclear localization, the nuclear import of HA-Sgk in permeabilized cells required ATP, cytoplasm, and a functional nuclear pore complex [4].
• Mutagenesis of lysines by alanine substitution defined a KKAILKKKEEK sequence within the central domain of Sgk between amino acids 131-141 that functions as a nuclear localization signal (NLS) required for the in vitro interaction with importin-alpha and for nuclear import of full-length Sgk in cultured cells [4].
• Our results establish that the subcellular distribution of Sgk is under stringent cell cycle and hormonal control [5].
• Sgk is localized to the perinuclear or cytoplasmic compartment as a 50-kDa hypophosphorylated protein in cells arrested in G1 by treatment with the synthetic glucocorticoid dexamethasone [5].
• In cells synchronously released from the G1/S boundary, Sgk localized to the nucleus during progression through S phase [5].

Biological context of Sgk

• Transient transfection of a mouse Sgk1 expression vector along with a -1590 NPR-A luciferase reporter resulted in an approximately 3-fold increment in reporter activity, which was significantly reduced by cotransfection with a kinase-dead Sgk1 mutant [6].
• In contrast, FSH induction and phosphorylation of Sgk protein requires A kinase (H89 sensitive) but also involves PI3-K (LY294002 sensitive) as well as p38MAPK (SB203580 sensitive) pathways [7].
• Alteration of serum/glucocorticoid regulated kinase-1 (sgk-1) gene expression in rat hippocampus after transient global ischemia [1].
• Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1 [2].
• Sgk mRNA exhibited a biphasic expression pattern, with maximal levels observed at 48 h of FSH/forskolin as granulosa cells differentiate to the preovulatory phenotype [8].

Anatomical context of Sgk

• Previous work in Xenopus laevis oocytes suggested that Sgk1 phosphorylates specific residues (Ser212 and Ser328) on the ubiquitin-protein ligase Nedd4-2, an enzyme that directly interacts with ENaC and negatively controls channel density at the plasma membrane [9].
• Using in situ hybridization (ISH) analysis, the increased level of sgk-1 gene expression was found to localize in pyramidal cells of CA2 and CA3 regions of the hippocampus after 2 h of reperfusion [1].
• Aldosterone can directly modulate podocyte function, possibly through the induction of oxidative stress and Sgk1 [2].
• Thus, either the mechanisms of nuclear import and export or the presence of distinct docking sites (and functions ?) dictate where A-kinase, phospho-CREB and Sgk are localized in granulosa cells compared with the terminally differentiated luteal cells [10].
• To analyze Sgk in functional corpora lutea, PRL was administered to HEF/hCG rats, or ovaries of pregnant rats were obtained on day 7, 15, or 22 of gestation [11].

Associations of Sgk with chemical compounds

• We conclude the increased expression of Sgk-1 in the cortical collecting tubules is a primary event in the early antinatriuretic and kaliuretic responses to physiologic concentrations of aldosterone [12].
• GILZ and alphaENaC transcripts were higher after treatment with either or both hormones, whereas the mRNA abundance of Sgk-1 was increased in the cortical collecting tubule by aldosterone but not by dexamethasone [12].
• Expression of serum/glucocorticoid-inducible kinase (Sgk), one member of an inducible serine/threonine kinase family, is induced by FSH/cAMP in rat granulosa cells cultured in defined medium [11].
• Altered psmb9, SGK, and Tap1 mRNA levels were also observed in an in vivo model of neuronal plasticity involving Zif268 induction: the effect of haloperidol administration on striatal gene expression [13].

Other interactions of Sgk

• Furthermore, aldosterone enhanced the expression of Sgk1, which was inhibited by mineralocorticoid receptor antagonist and tempol [2].
• Aromatase, Sgk, and phospho-CREB were expressed at elevated levels in a non-forskolin-responsive manner [10].

Analytical, diagnostic and therapeutic context of Sgk

• Using high-density oligonucleotide array analysis, we found that the sgk-1 gene was one of the genes showing alteration of expression in the rat hippocampus during 1-4 h of reperfusion after 10 min of transient global cerebral ischemia [1].
• Using TaqMan RT-PCR analysis, we confirmed an increased level of sgk-1 gene expression with statistical significance in the rat hippocampus at 2 h of reperfusion after 10 min of transient global cerebral ischemia [1].
• Laser scanning cytometry, which monitors Sgk localization and DNA content in individual mammary tumor cells of an asynchronously growing population, revealed that Sgk actively shuttles between the nucleus (in S and G2/M) and the cytoplasm (in G1) in synchrony with the cell cycle [5].
• When the subcellular localization of this kinase was analyzed by immunohistochemistry, Sgk protein was nuclear in granulosa cells and some thecal cells of large preovulatory follicles [11].
• Steady state mRNA of ENaC subunits alpha, beta, gamma serum and glucocorticoid inducible kinase (Sgk1) were measured by TaqMan PCR in kidney homogenates at week 1, 2, 3 and 4 after BDL [14].

References