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SGK1 (serum/glucocorticoid regulated kinase 1)

Written2014-09Miranda Menniti, Rodolfo Iuliano, Lucia D'Antona, Cristina Talarico, Rosario Amato, Nicola Perrotti
Dipartimento di Scienze della Salute, Universita degli Studi Magna Graecia di Catanzaro (MM, RA, NP); Dipartimento di Medicina Sperimentale e Clinica, Universita degli Studi Magna Graecia di Catanzaro (RI, LDA,CT)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSGK
serum/glucocorticoid regulated kinase
Other alias
HGNC (Hugo) SGK1
LocusID (NCBI) 6446
Atlas_Id 42281
Location 6q23.2  [Link to chromosome band 6q23]
Location_base_pair Starts at 134169246 and ends at 134318058 bp from pter ( according to hg19-Feb_2009)  [Mapping SGK1.png]
Fusion genes
(updated 2016)
CD74 (5q32) / SGK1 (6q23.2)CDC42BPA (1q42.13) / SGK1 (6q23.2)FGF13 (Xq26.3) / SGK1 (6q23.2)
KIF3C (2p23.3) / SGK1 (6q23.2)LOC100507412 (-) / SGK1 (6q23.2)PLP1 (Xq22.2) / SGK1 (6q23.2)
SGK1 (6q23.2) / IGFBP4 (17q21.2)SGK1 (6q23.2) / NUFIP2 (17q11.2)SGK1 (6q23.2) / SGK1 (6q23.2)
SLC2A12 (6q23.2) / SGK1 (6q23.2)

DNA/RNA

Description The SGK1 gene is comprised of 14 coding exons (Ensembl).
Transcription Sgk1 contains 28 distinct gt-ag introns, it presents 32 different mRNAs transcription products with 28 alternatively spliced variants and 4 unspliced forms. 8 probable alternative promoters have been identified, 10 non overlapping alternative last exons and 8 validated alternative polyadenylation sites (AceView).
The SGK1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and C. elegans (Gene ID: 6446, NCBI).

Protein

Note The serum- and glucocorticoid-inducible kinase 1 (SGK1) was discovered as a gene regulated transcriptionally by serum- and glucocorticoids in rat mammary tumor cells (Firestone et al., 2003).
 
  Chain (1-431) serine/threonine-protein kinase Sgk1; domain (98-355) protein kinase; domain (366-431) AGC-kinase C-terminal (UNIPROT).
Description SGK1 is a member of the "AGC" subfamily (García Martínez and Alessi, 2008). SGK1 activation is dependent on phosphorylation. mTOR was found to be the H-motif kinase that phosphorylates Sgk1 at S422 and PDK1 at T256 (Hong et al., 2008; Amato et al., 2007; Kobayashi and Cohen, 1999; Perrotti et al., 2001).
Sgk1 is involved in mediating growth factor-, insulin-, IL-2- and steroid-dependent survival signals (Lang et al., 2009a; Mikosz et al., 2001).
Expression SGK1 transcription is regulated by the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), the progesterone receptor (PR), the vitamin D receptor (VDR), the retinoid X receptor (RXR), the farnesoid X receptor (FXR), the sterol regulatory element binding protein (SREBP), peroxisome proliferator-activated receptor γ (PPARγ), the cAMP response element binding protein (CREB), the p53 tumor suppressor protein, the Sp1 transcription factor, the activating protein 1 (AP1), the activating transcription factor 6 (ATF6), the heat shock factor (HSF), reticuloendotheliosis viral oncogene homolog (c-Rel), nuclear factor κB (NFκB), signal transducers and activators of transcription (STAT), TGFβ dependent transcription factors SMAD3 and SMAD4, and fork-head activin signal transducer (FAST) (Lang et al., 2009a).
Localisation SGK presents a stimulus-dependent regulation for the subcellular localization. SGK actively shuttles between the nucleus (in S and G2/M) and the cytoplasm (in G1) in synchrony with the cell cycle (Buse et al., 1999). The nuclear localization signal (NLS) of SGK (located at an external surface of the molecule) binds the importin-alpha nuclear import receptor regulating the nuclear-cytoplasmic shuttling (Firestone et al., 2003).
SGK-1 localizes in the mitochondria, under hyperosmotic stress, that permits access to physiologically appropriate mitochondrial interacting proteins and substrates, such as IF-1 and the F1F0-ATPase, as part of the cellular stressed induced program (O'Keeffe et al., 2013).
A significant fraction of SGK-1 is membrane-associated and ubiquitilated (Brickley et al., 2002).
Function SGK1 regulates different ion channels, transporters, transcription factors and enzyme: ion channels like ENaC (Faletti et al., 2002), TRPV5, ROMK, Kv1.3, KCNE1/KCNQ1, GluR1, GluR6; carriers like NHE3, GLUT1, SGLT1, EAAT1, EAAT2, EAAT3, EAAT4, EAAT5, Na+-K+-ATPase. SGK1 regulates the activity of enzymes like glycogen synthase kinase-3, ubiquitin ligase Nedd4-2, phosphomannomutase-2 and transcription factors like forkhead transcription factor FKHRL1, beta-catenin, nuclear factor kappaB. Moreover, SGK1 contributes to the regulation of transport, hormone release, neuroexcitability, cell proliferation, and apoptosis (Lang et al., 2006).
Sgk1 can phosphorylate and activate MDM2, driving p53 to degradation, protecting cells from stress dependent apoptosis (Amato et al., 2009).
Sgk1 was demonstrated to interact with phosphomannomutase 2 (PMM2), inhibiting its activity, with and without insulin stimulus (Menniti et al., 2005). Moreover, it was demonstrated that the 60 kDa Lysophospholipase (LysoLP) interacts with SGK1, and that the expression of LysoLP in Xenopus oocytes decreases membrane expression of ENaC, inhibiting basal and Sgk1-dependent activation of the channel (Menniti et al., 2010). Sgk1 can regulates RANBP1 at the gene transcription level with functional consequences on microtubule stability and cell sensitivity to taxol (Amato et al., 2013).
Alternative initiation of transcription at -2981, -850 upstream of the transcription initiation site (+1) of the reference mRNA of SGK1 was studied. Transcription of three distinct splice variants are all markedly upregulated in tumor tissues but differentially up-regulated under differentiation or hypoxia.

Implicated in

Note
  
Entity Various cancers
Note Increased expression of SGK1 have been observed in colon cancer, myeloma, medulloblastoma, prostate cancer, ovarian tumors and non-small cell lung cancer (Lang et al., 2013).
SGK1-sensitive implication in tumour growth include activation of K(+) channels and Ca(2+) channels, Na(+)/H(+) exchanger, amino acid transporters, glucose transporters, upregulation of the nuclear factor NFkappaB and beta-catenin and downregulation of the transcription factors Foxo3a/FKHRL1 and p53 (Lang et al., 2010).
SGK1 phosphorylates MDM2 with consequent p53 ubiquitylation, and influences cell proliferation, survival, and differentiation (Amato et al., 2009).
In cancer cells, SGK1 up-regulates RanBP1, a major effector of the GTPase RAN, which in turn influences mitotic microtubule activity and decreases taxol sensitivity (Amato et al., 2013).
SGK1 expression mediated the phosphorylation of ERK2, then the MEK/ERK complexes formation during liver regeneration (Won et al., 2009).
SGK1 negatively regulates stress-activated signaling through inhibition of SEK1 function (Kim et al., 2007).
SGK1 interferes with the binding of SEK1 to JNK1 and MEKK1 (Lang et al., 2010), down-regulates vinculin phosphorylation, which in turn may enhance migration via actin cytoskeleton redistribution (Schmidt et al., 2012).
SGK1 influences the activity of channels and transporters, such as Ca2+ release-activated channels (ICRAC) Orai1/STIM (Eylenstein et al., 2012) and the K+ channel Kv1.3, influencing cell proliferation and cell death (Schmidt et al., 2012).
SGK1 is a direct beta-catenin target gene and in colon cancer cells its up-regulation determines a decrease of apoptosis through the down-regulation of Foxo3a activity (Dehner et al., 2008).
SGK-1 has significant homology with the serine-threonine Akt which is considered a relevant player in carcinogenesis, since its activation occurred in the majority of human tumors. Interestingly, some cancer cell lines that are resistant to Akt inhibition showed significant up-regulation of SGK1 expression (Sommer et al., 2013).
  
  
Entity Colorectal carcinoma
Note A recent study confirms the sensitivity of colon carcinoma to the expression of SGK1. Following deficiency of APC (adenoma polyposis coli) or chemical cancerogenesis, SGK1 knockout mice develop less intestinal tumours than their wild-type littermates and pharmacological SGK1 inhibition counteracts growth of cancer cells (Lang et al., 2010). SGK1 up-regulates RanBP1, a major effector of the GTPase RAN, which in turn influences mitotic microtubule activity and decreases taxol sensitivity in RKO colon carcinoma cells (Amato et al., 2013).
  
  
Entity Kidney cancer
Note In A-498 kidney cancer cells, IL-2 binding to its own receptor triggers a signal transduction pathway leading to the inhibition of proliferation and apoptosis. Inhibition of proliferation is associated with Erk1/2 dephosphorylation, whereas the survival signals appear to be mediated by Sgk1 activation (Amato et al., 2007).
  
  
Entity Myeloma
Note SGK1 is a highly cytokine-responsive gene in myeloma cells promoting their malignant growth. Fagerli et al. recently have demonstrated a rapid, strong and sustained induction of SGK1 in primary myeloma cells. Inhibition of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway abolished STAT3 phosphorylation and SGK1 induction. Downregulation of SGK1 by shRNAs resulted in decreased proliferation of myeloma cell lines, with induction of cell cycle inhibitory genes, like CDKNA1/p21, and downregulation of CDK6 and RBL2/p130 (Fagerli et al., 2011).
  
  
Entity Prostate cancer
Note Rauhala et al. showed the downregulation of mRNA and protein expressions of SGK, in prostate cancer. The expression of SGK was decreased in about half of the prostate carcinomas, whereas the expression was high in all non-malignant prostate epithelial cells (Rauhala et al., 2005).
Low espression of SGK1 is associated with higher tumor grade and increased cancer recurrence, and is a potential indicator of aberrant androgen receptor signaling. Glucocorticoid receptor expression increased with androgen deprivation, potentially providing a mechanism forthe maintenance of androgen pathway signaling in these tumors (Szmulewitz et al., 2012).
Inhibition of SGK1 expression or activity antagonizes androgen-induced growth of the prostate cancer cell line LNCaP, suggesting that SGK1 might be a viable target for the treatment of prostate cancer (Sherk et al., 2008).
  
  
Entity Ovarian cancer
Note Sgk was identified like a critical FSH-regulated gene important for the proliferation and maturation of granulosa cells in the normal ovary (Richards, 1994).
Specific and reproducible gene expression changes occur in human ovarian tumors over time, following systemic administration of glucocorticoids. Induction of SGK1 gene expression in epithelial tumor cell lines inhibits chemotherapy-induced tumor cell apoptosis (Melhem et al., 2009).
Sgk expression is lower in epithelial tumours, serous and mucinous cystadenocarcinomas, and also in normal pre-menopausal ovaries (Chu et al., 2002).
  
  
Entity Hypertension
Note There are different SGK1 gene variants that can influence blood pressure (Rao et al., 2013), including the combination of polymorphisms in intron 6 [I6CC] and exon 8 [E8CC/CT] (Lang et al., 2006; Lang et al., 2009a).
The insulin probably stimulates renal tubular salt reabsorption through the activation of SGK1 with consequent renal salt retention and hypertension in type II diabetes (Lang et al., 2006; Lang et al., 2009a).
  
  
Entity Diabetes
Note SGK1 regulates the Na+ coupled glucose transporter SGLT1 (Lang et al., 2006), the adipocyte differentiation and the adipogenesis (Di Pietro et al., 2010). The I6CC/E8CC/CT SGK1 gene variant determines enhancement in body weight and prevalence of type 2 diabetes (Lang et al., 2009b).
  
  
Entity Thrombosis
Note SGK1 stimulates coagulation, through tissue factor expression (Lang et al., 2009a) and regulation of blood platelets by up-regulation of NFκB, and consequent expression of the platelet Ca2+ channel Orai1/STIM1, that predisposing to stroke (Dahlberg et al., 2011) and thrombosis (Borst et al., 2012).
  
  
Entity Autoimmune disease
Note SGK1 is involved in autoimmune disease, through up-regulation of the pathogenic IL-23-dependent interleukin (IL) 17-producing CD4+ helper T cells (TH17 cells) (Kleinewietfeld et al., 2013).
In affected tissues of inflammatory and fibrosing diseases was demonstrated an excessive expression of SGK1, like in lung fibrosis, diabetic nephropathy, glomerulonephritis, experimental nephrotic syndrome, obstructive nephropathy, liver scirrhosis, fibrosing pancreatitis, peritoneal fibrosis, Crohn's disease, and coeliac disease (Cheng et al., 2010; Lang et al., 2006; Yamahara et al., 2009).
  

Bibliography

Sgk1 activates MDM2-dependent p53 degradation and affects cell proliferation, survival, and differentiation.
Amato R, D'Antona L, Porciatti G, Agosti V, Menniti M, Rinaldo C, Costa N, Bellacchio E, Mattarocci S, Fuiano G, Soddu S, Paggi MG, Lang F, Perrotti N.
J Mol Med (Berl). 2009 Dec;87(12):1221-39. doi: 10.1007/s00109-009-0525-5. Epub 2009 Sep 11.
PMID 19756449
 
IL-2 signals through Sgk1 and inhibits proliferation and apoptosis in kidney cancer cells.
Amato R, Menniti M, Agosti V, Boito R, Costa N, Bond HM, Barbieri V, Tagliaferri P, Venuta S, Perrotti N.
J Mol Med (Berl). 2007 Jul;85(7):707-21. Epub 2007 Jun 15.
PMID 17571248
 
Sgk1 enhances RANBP1 transcript levels and decreases taxol sensitivity in RKO colon carcinoma cells.
Amato R, Scumaci D, D'Antona L, Iuliano R, Menniti M, Di Sanzo M, Faniello MC, Colao E, Malatesta P, Zingone A, Agosti V, Costanzo FS, Mileo AM, Paggi MG, Lang F, Cuda G, Lavia P, Perrotti N.
Oncogene. 2013 Sep 19;32(38):4572-8. doi: 10.1038/onc.2012.470. Epub 2012 Oct 29.
PMID 23108393
 
Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis.
Anacker C, Cattaneo A, Musaelyan K, Zunszain PA, Horowitz M, Molteni R, Luoni A, Calabrese F, Tansey K, Gennarelli M, Thuret S, Price J, Uher R, Riva MA, Pariante CM.
Proc Natl Acad Sci U S A. 2013 May 21;110(21):8708-13. doi: 10.1073/pnas.1300886110. Epub 2013 May 6.
PMID 23650397
 
A novel N-terminal hydrophobic motif mediates constitutive degradation of serum- and glucocorticoid-induced kinase-1 by the ubiquitin-proteasome pathway.
Bogusz AM, Brickley DR, Pew T, Conzen SD.
FEBS J. 2006 Jul;273(13):2913-28.
PMID 16817852
 
The serum- and glucocorticoid-inducible kinase 1 (SGK1) influences platelet calcium signaling and function by regulation of Orai1 expression in megakaryocytes.
Borst O, Schmidt EM, Munzer P, Schonberger T, Towhid ST, Elvers M, Leibrock C, Schmid E, Eylenstein A, Kuhl D, May AE, Gawaz M, Lang F.
Blood. 2012 Jan 5;119(1):251-61. doi: 10.1182/blood-2011-06-359976. Epub 2011 Oct 26.
PMID 22031864
 
Ubiquitin modification of serum and glucocorticoid-induced protein kinase-1 (SGK-1).
Brickley DR, Mikosz CA, Hagan CR, Conzen SD.
J Biol Chem. 2002 Nov 8;277(45):43064-70. Epub 2002 Sep 5.
PMID 12218062
 
Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a).
Brunet A, Park J, Tran H, Hu LS, Hemmings BA, Greenberg ME.
Mol Cell Biol. 2001 Feb;21(3):952-65.
PMID 11154281
 
Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum- and glucocorticoid-inducible protein kinase, Sgk, in mammary tumor cells. A novel convergence point of anti-proliferative and proliferative cell signaling pathways.
Buse P, Tran SH, Luther E, Phu PT, Aponte GW, Firestone GL.
J Biol Chem. 1999 Mar 12;274(11):7253-63.
PMID 10066787
 
Rescue of DeltaF508-CFTR by the SGK1/Nedd4-2 signaling pathway.
Caohuy H, Jozwik C, Pollard HB.
J Biol Chem. 2009 Sep 11;284(37):25241-53. doi: 10.1074/jbc.M109.035345. Epub 2009 Jul 17.
PMID 19617352
 
Serum and glucocorticoid-inducible kinase 1 (SGK1) is necessary for vascular remodeling during angiogenesis.
Catela C, Kratsios P, Hede M, Lang F, Rosenthal N.
Dev Dyn. 2010 Aug;239(8):2149-60. doi: 10.1002/dvdy.22345.
PMID 20568246
 
Serum- and glucocorticoid-regulated kinase 1 is upregulated following unilateral ureteral obstruction causing epithelial-mesenchymal transition.
Cheng J, Truong LD, Wu X, Kuhl D, Lang F, Du J.
Kidney Int. 2010 Oct;78(7):668-78. doi: 10.1038/ki.2010.214. Epub 2010 Jul 14.
PMID 20631674
 
FSH-regulated gene expression profiles in ovarian tumours and normal ovaries.
Chu S, Rushdi S, Zumpe ET, Mamers P, Healy DL, Jobling T, Burger HG, Fuller PJ.
Mol Hum Reprod. 2002 May;8(5):426-33.
PMID 11994539
 
Genetic variants in serum and glucocortocoid regulated kinase 1, a regulator of the epithelial sodium channel, are associated with ischaemic stroke.
Dahlberg J, Smith G, Norrving B, Nilsson P, Hedblad B, Engstrom G, Lovkvist H, Carlson J, Lindgren A, Melander O.
J Hypertens. 2011 May;29(5):884-9. doi: 10.1097/HJH.0b013e3283455117.
PMID 21430556
 
Wnt signaling inhibits Forkhead box O3a-induced transcription and apoptosis through up-regulation of serum- and glucocorticoid-inducible kinase 1.
Dehner M, Hadjihannas M, Weiske J, Huber O, Behrens J.
J Biol Chem. 2008 Jul 11;283(28):19201-10. doi: 10.1074/jbc.M710366200. Epub 2008 May 16.
PMID 18487207
 
Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates adipocyte differentiation via forkhead box O1.
Di Pietro N, Panel V, Hayes S, Bagattin A, Meruvu S, Pandolfi A, Hugendubler L, Fejes-Toth G, Naray-Fejes-Toth A, Mueller E.
Mol Endocrinol. 2010 Feb;24(2):370-80. doi: 10.1210/me.2009-0265. Epub 2009 Dec 4.
PMID 19965929
 
The N-terminus of the serum- and glucocorticoid-inducible kinase Sgk1 specifies mitochondrial localization and rapid turnover.
Engelsberg A, Kobelt F, Kuhl D.
Biochem J. 2006 Oct 1;399(1):69-76.
PMID 16776652
 
Transcription factor NF-kB regulates expression of pore-forming Ca2+ channel unit, Orai1, and its activator, STIM1, to control Ca2+ entry and affect cellular functions.
Eylenstein A, Schmidt S, Gu S, Yang W, Schmid E, Schmidt EM, Alesutan I, Szteyn K, Regel I, Shumilina E, Lang F.
J Biol Chem. 2012 Jan 20;287(4):2719-30. doi: 10.1074/jbc.M111.275925. Epub 2011 Nov 21.
PMID 22110130
 
Serum/glucocorticoid-regulated kinase 1 (SGK1) is a prominent target gene of the transcriptional response to cytokines in multiple myeloma and supports the growth of myeloma cells.
Fagerli UM, Ullrich K, Stuhmer T, Holien T, Kochert K, Holt RU, Bruland O, Chatterjee M, Nogai H, Lenz G, Shaughnessy JD Jr, Mathas S, Sundan A, Bargou RC, Dorken B, Borset M, Janz M.
Oncogene. 2011 Jul 14;30(28):3198-206. doi: 10.1038/onc.2011.79. Epub 2011 Apr 11.
PMID 21478911
 
sgk: an essential convergence point for peptide and steroid hormone regulation of ENaC-mediated Na+ transport.
Faletti CJ, Perrotti N, Taylor SI, Blazer-Yost BL.
Am J Physiol Cell Physiol. 2002 Mar;282(3):C494-500.
PMID 11832334
 
SGK1-mediated fibronectin formation in diabetic nephropathy.
Feng Y, Wang Q, Wang Y, Yard B, Lang F.
Cell Physiol Biochem. 2005;16(4-6):237-44.
PMID 16301823
 
Stimulus-dependent regulation of serum and glucocorticoid inducible protein kinase (SGK) transcription, subcellular localization and enzymatic activity.
Firestone GL, Giampaolo JR, O'Keeffe BA.
Cell Physiol Biochem. 2003;13(1):1-12. (REVIEW)
PMID 12649597
 
mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1).
Garcia-Martinez JM, Alessi DR.
Biochem J. 2008 Dec 15;416(3):375-85. doi: 10.1042/BJ20081668.
PMID 18925875
 
mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation.
Hong F, Larrea MD, Doughty C, Kwiatkowski DJ, Squillace R, Slingerland JM.
Mol Cell. 2008 Jun 20;30(6):701-11. doi: 10.1016/j.molcel.2008.04.027.
PMID 18570873
 
Negative regulation of SEK1 signaling by serum- and glucocorticoid-inducible protein kinase 1.
Kim MJ, Chae JS, Kim KJ, Hwang SG, Yoon KW, Kim EK, Yun HJ, Cho JH, Kim J, Kim BW, Kim HC, Kang SS, Lang F, Cho SG, Choi EJ.
EMBO J. 2007 Jul 11;26(13):3075-85. Epub 2007 Jun 14.
PMID 17568772
 
Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells.
Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA.
Nature. 2013 Apr 25;496(7446):518-22. doi: 10.1038/nature11868. Epub 2013 Mar 6.
PMID 23467095
 
Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2.
Kobayashi T, Cohen P.
Biochem J. 1999 Apr 15;339 ( Pt 2):319-28.
PMID 10191262
 
The physiological impact of the serum and glucocorticoid-inducible kinase SGK1.
Lang F, Artunc F, Vallon V.
Curr Opin Nephrol Hypertens. 2009a Sep;18(5):439-48. doi: 10.1097/MNH.0b013e32832f125e. (REVIEW)
PMID 19584721
 
(Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms.
Lang F, Bohmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V.
Physiol Rev. 2006 Oct;86(4):1151-78. (REVIEW)
PMID 17015487
 
Targeting SGK1 in diabetes.
Lang F, Gorlach A, Vallon V.
Expert Opin Ther Targets. 2009b Nov;13(11):1303-11. doi: 10.1517/14728220903260807. (REVIEW)
PMID 19764891
 
Colorectal carcinoma cells--regulation of survival and growth by SGK1.
Lang F, Perrotti N, Stournaras C.
Int J Biochem Cell Biol. 2010 Oct;42(10):1571-5. doi: 10.1016/j.biocel.2010.05.016. Epub 2010 Jun 9. (REVIEW)
PMID 20541034
 
Serum and glucocorticoid inducible kinase, metabolic syndrome, inflammation, and tumor growth.
Lang F, Stournaras C.
Hormones (Athens). 2013 Apr-Jun;12(2):160-71. (REVIEW)
PMID 23933686
 
Importin-alpha mediates the regulated nuclear targeting of serum- and glucocorticoid-inducible protein kinase (Sgk) by recognition of a nuclear localization signal in the kinase central domain.
Maiyar AC, Leong ML, Firestone GL.
Mol Biol Cell. 2003 Mar;14(3):1221-39.
PMID 12631736
 
Phosphorylation of NDRG1 is temporally and spatially controlled during the cell cycle.
McCaig C, Potter L, Abramczyk O, Murray JT.
Biochem Biophys Res Commun. 2011 Jul 29;411(2):227-34. doi: 10.1016/j.bbrc.2011.06.092. Epub 2011 Jun 17.
PMID 21708134
 
Administration of glucocorticoids to ovarian cancer patients is associated with expression of the anti-apoptotic genes SGK1 and MKP1/DUSP1 in ovarian tissues.
Melhem A, Yamada SD, Fleming GF, Delgado B, Brickley DR, Wu W, Kocherginsky M, Conzen SD.
Clin Cancer Res. 2009 May 1;15(9):3196-204. doi: 10.1158/1078-0432.CCR-08-2131. Epub 2009 Apr 21.
PMID 19383827
 
60kDa lysophospholipase, a new Sgk1 molecular partner involved in the regulation of ENaC.
Menniti M, Iuliano R, Foller M, Sopjani M, Alesutan I, Mariggio S, Nofziger C, Perri AM, Amato R, Blazer-Yost B, Corda D, Lang F, Perrotti N.
Cell Physiol Biochem. 2010;26(4-5):587-96. doi: 10.1159/000322326. Epub 2010 Oct 29.
PMID 21063096
 
Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1.
Mikosz CA, Brickley DR, Sharkey MS, Moran TW, Conzen SD.
J Biol Chem. 2001 May 18;276(20):16649-54. Epub 2001 Feb 13.
PMID 11278764
 
The serum- and glucocorticoid-induced protein kinase-1 (Sgk-1) mitochondria connection: identification of the IF-1 inhibitor of the F(1)F(0)-ATPase as a mitochondria-specific binding target and the stress-induced mitochondrial localization of endogenous Sgk-1.
O'Keeffe BA1, Cilia S, Maiyar AC, Vaysberg M, Firestone GL.
Biochimie. 2013 Jun;95(6):1258-65. doi: 10.1016/j.biochi.2013.01.019. Epub 2013 Feb 8.
PMID 23402912
 
Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin.
Perrotti N, He RA, Phillips SA, Haft CR, Taylor SI.
J Biol Chem. 2001 Mar 23;276(12):9406-12. Epub 2000 Nov 28.
PMID 11096081
 
Rapid aldosterone actions on epithelial sodium channel trafficking and cell proliferation.
Quinn S, Harvey BJ, Thomas W.
Steroids. 2014 Mar;81:43-8. doi: 10.1016/j.steroids.2013.11.005. Epub 2013 Nov 20.
PMID 24269741
 
Polymorphisms in the serum- and glucocorticoid-inducible kinase 1 gene are associated with blood pressure and renin response to dietary salt intake.
Rao AD, Sun B, Saxena A, Hopkins PN, Jeunemaitre X, Brown NJ, Adler GK, Williams JS.
J Hum Hypertens. 2013 Mar;27(3):176-80. doi: 10.1038/jhh.2012.22. Epub 2012 May 31.
PMID 22648267
 
Dual-specificity phosphatase 1 and serum/glucocorticoid-regulated kinase are downregulated in prostate cancer.
Rauhala HE, Porkka KP, Tolonen TT, Martikainen PM, Tammela TL, Visakorpi T.
Int J Cancer. 2005 Dec 10;117(5):738-45.
PMID 15981206
 
Serum- and glucocorticoid-regulated kinase isoform-1 and epithelial sodium channel subunits in human ocular ciliary epithelium.
Rauz S, Walker EA, Hughes SV, Coca-Prados M, Hewison M, Murray PI, Stewart PM.
Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1643-51.
PMID 12657604
 
Hormonal control of gene expression in the ovary.
Richards JS.
Endocr Rev. 1994 Dec;15(6):725-51. (REVIEW)
PMID 7705279
 
Serum- and glucocorticoid-inducible kinase SGK1 regulates reorganization of actin cytoskeleton in mast cells upon degranulation.
Schmid E, Gu S, Yang W, Munzer P, Schaller M, Lang F, Stournaras C, Shumilina E.
Am J Physiol Cell Physiol. 2013 Jan 1;304(1):C49-55. doi: 10.1152/ajpcell.00179.2012. Epub 2012 Sep 26.
PMID 23015548
 
Serum- and glucocorticoid-dependent kinase-1-induced cell migration is dependent on vinculin and regulated by the membrane androgen receptor.
Schmidt EM, Gu S, Anagnostopoulou V, Alevizopoulos K, Foller M, Lang F, Stournaras C.
FEBS J. 2012 Apr;279(7):1231-42. doi: 10.1111/j.1742-4658.2012.08515.x. Epub 2012 Feb 24.
PMID 22309306
 
Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic.
Sherk AB, Frigo DE, Schnackenberg CG, Bray JD, Laping NJ, Trizna W, Hammond M, Patterson JR, Thompson SK, Kazmin D, Norris JD, McDonnell DP.
Cancer Res. 2008 Sep 15;68(18):7475-83. doi: 10.1158/0008-5472.CAN-08-1047.
PMID 18794135
 
Differential regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) splice variants based on alternative initiation of transcription.
Simon P, Schneck M, Hochstetter T, Koutsouki E, Mittelbronn M, Merseburger A, Weigert C, Niess A, Lang F.
Cell Physiol Biochem. 2007;20(6):715-28.
PMID 17982254
 
Elevated SGK1 predicts resistance of breast cancer cells to Akt inhibitors.
Sommer EM, Dry H, Cross D, Guichard S, Davies BR, Alessi DR.
Biochem J. 2013 Jun 15;452(3):499-508. doi: 10.1042/BJ20130342.
PMID 23581296
 
The interdependence of EGF-R and SGK-1 in fibronectin expression in primary kidney cortical fibroblast cells.
Stevens VA, Saad S, Chen XM, Pollock CA.
Int J Biochem Cell Biol. 2007;39(5):1047-54. Epub 2007 Feb 23.
PMID 17382577
 
Serum/glucocorticoid-regulated kinase 1 expression in primary human prostate cancers.
Szmulewitz RZ, Chung E, Al-Ahmadie H, Daniel S, Kocherginsky M, Razmaria A, Zagaja GP, Brendler CB, Stadler WM, Conzen SD.
Prostate. 2012 Feb 1;72(2):157-64. doi: 10.1002/pros.21416. Epub 2011 May 11.
PMID 21563193
 
SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF-kappaB activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B expression.
Tai DJ, Su CC, Ma YL, Lee EH.
J Biol Chem. 2009 Feb 13;284(7):4073-89. doi: 10.1074/jbc.M805055200. Epub 2008 Dec 16.
PMID 19088076
 
Ablation of the mTORC2 component rictor in brain or Purkinje cells affects size and neuron morphology.
Thomanetz V, Angliker N, Cloetta D, Lustenberger RM, Schweighauser M, Oliveri F, Suzuki N, Ruegg MA.
J Cell Biol. 2013 Apr 15;201(2):293-308. doi: 10.1083/jcb.201205030. Epub 2013 Apr 8.
PMID 23569215
 
mTOR and Akt signaling in cancer: SGK cycles in.
Toker A.
Mol Cell. 2008 Jul 11;31(1):6-8. doi: 10.1016/j.molcel.2008.06.007.
PMID 18614042
 
Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates glucocorticoid-induced inhibition of insulin secretion.
Ullrich S, Berchtold S, Ranta F, Seebohm G, Henke G, Lupescu A, Mack AF, Chao CM, Su J, Nitschke R, Alexander D, Friedrich B, Wulff P, Kuhl D, Lang F.
Diabetes. 2005 Apr;54(4):1090-9.
PMID 15793248
 
Induction of serum- and glucocorticoid-induced kinase-1 (SGK1) by cAMP regulates increases in alpha-ENaC.
Vasquez MM, Castro R, Seidner SR, Henson BM, Ashton DJ, Mustafa SB.
J Cell Physiol. 2008 Dec;217(3):632-42. doi: 10.1002/jcp.21534.
PMID 18615584
 
Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration.
Won M, Park KA, Byun HS, Kim YR, Choi BL, Hong JH, Park J, Seok JH, Lee YH, Cho CH, Song IS, Kim YK, Shen HM, Hur GM.
J Hepatol. 2009 Jul;51(1):67-76. doi: 10.1016/j.jhep.2009.02.027. Epub 2009 Apr 16.
PMID 19447520
 
Direct aldosterone action as a profibrotic factor via ROS-mediated SGK1 in peritoneal fibroblasts.
Yamahara H, Kishimoto N, Nakata M, Okazaki A, Kimura T, Sonomura K, Matsuoka E, Shiotsu Y, Adachi T, Matsubara H, Iwasaka T, Mori Y.
Kidney Blood Press Res. 2009;32(3):185-93. doi: 10.1159/000225379. Epub 2009 Jun 12.
PMID 19521108
 
p53-dependent inhibition of FKHRL1 in response to DNA damage through protein kinase SGK1.
You H, Jang Y, You-Ten AI, Okada H, Liepa J, Wakeham A, Zaugg K, Mak TW.
Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14057-62. Epub 2004 Sep 21.
PMID 15383658
 
Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.
Zhang BH, Tang ED, Zhu T, Greenberg ME, Vojtek AB, Guan KL.
J Biol Chem. 2001 Aug 24;276(34):31620-6. Epub 2001 Jun 15.
PMID 11410590
 

Citation

This paper should be referenced as such :
Menniti M, Iuliano R, D'Antona L, Talarico C, Amato R, Perrotti N
SGK1 (serum/glucocorticoid regulated kinase 1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/SGK1ID42281ch6q23.html


External links

Nomenclature
HGNC (Hugo)SGK1   10810
Cards
AtlasSGK1ID42281ch6q23
Entrez_Gene (NCBI)SGK1  6446  serum/glucocorticoid regulated kinase 1
AliasesSGK
GeneCards (Weizmann)SGK1
Ensembl hg19 (Hinxton)ENSG00000118515 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000118515 [Gene_View]  chr6:134169246-134318058 [Contig_View]  SGK1 [Vega]
ICGC DataPortalENSG00000118515
TCGA cBioPortalSGK1
AceView (NCBI)SGK1
Genatlas (Paris)SGK1
WikiGenes6446
SOURCE (Princeton)SGK1
Genetics Home Reference (NIH)SGK1
Genomic and cartography
GoldenPath hg38 (UCSC)SGK1  -     chr6:134169246-134318058 -  6q23.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SGK1  -     6q23.2   [Description]    (hg19-Feb_2009)
EnsemblSGK1 - 6q23.2 [CytoView hg19]  SGK1 - 6q23.2 [CytoView hg38]
Mapping of homologs : NCBISGK1 [Mapview hg19]  SGK1 [Mapview hg38]
OMIM602958   
Gene and transcription
Genbank (Entrez)AF153609 AK055077 AK098509 AK293383 AK295422
RefSeq transcript (Entrez)NM_001143676 NM_001143677 NM_001143678 NM_001291995 NM_005627
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SGK1
Cluster EST : UnigeneHs.510078 [ NCBI ]
CGAP (NCI)Hs.510078
Alternative Splicing GalleryENSG00000118515
Gene ExpressionSGK1 [ NCBI-GEO ]   SGK1 [ EBI - ARRAY_EXPRESS ]   SGK1 [ SEEK ]   SGK1 [ MEM ]
Gene Expression Viewer (FireBrowse)SGK1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6446
GTEX Portal (Tissue expression)SGK1
Protein : pattern, domain, 3D structure
UniProt/SwissProtO00141   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO00141  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO00141
Splice isoforms : SwissVarO00141
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusO00141
Domaine pattern : Prosite (Expaxy)AGC_KINASE_CTER (PS51285)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)AGC-kinase_C    Kinase-like_dom    Pkinase_C    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)Pkinase (PF00069)    Pkinase_C (PF00433)   
Domain families : Pfam (NCBI)pfam00069    pfam00433   
Domain families : Smart (EMBL)S_TK_X (SM00133)  S_TKc (SM00220)  
Conserved Domain (NCBI)SGK1
DMDM Disease mutations6446
Blocks (Seattle)SGK1
PDB (SRS)2R5T    3HDM    3HDN   
PDB (PDBSum)2R5T    3HDM    3HDN   
PDB (IMB)2R5T    3HDM    3HDN   
PDB (RSDB)2R5T    3HDM    3HDN   
Structural Biology KnowledgeBase2R5T    3HDM    3HDN   
SCOP (Structural Classification of Proteins)2R5T    3HDM    3HDN   
CATH (Classification of proteins structures)2R5T    3HDM    3HDN   
SuperfamilyO00141
Human Protein AtlasENSG00000118515
Peptide AtlasO00141
HPRD04264
IPIIPI00297590   IPI00479349   IPI00514242   IPI00645903   IPI00917765   IPI00977317   IPI00384994   IPI00976766   IPI00983318   IPI00984497   
Protein Interaction databases
DIP (DOE-UCLA)O00141
IntAct (EBI)O00141
FunCoupENSG00000118515
BioGRIDSGK1
STRING (EMBL)SGK1
ZODIACSGK1
Ontologies - Pathways
QuickGOO00141
Ontology : AmiGOregulation of cell growth  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine/tyrosine kinase activity  calcium channel regulator activity  protein binding  ATP binding  nucleus  cytoplasm  mitochondrion  endoplasmic reticulum membrane  cytosol  cytosol  plasma membrane  protein phosphorylation  sodium ion transport  apoptotic process  response to stress  cellular response to DNA damage stimulus  long-term memory  regulation of blood pressure  potassium channel regulator activity  nuclear speck  sodium channel regulator activity  chloride channel regulator activity  peptidyl-serine phosphorylation  regulation of cell migration  positive regulation of transporter activity  ion transmembrane transport  intracellular signal transduction  regulation of cell proliferation  regulation of apoptotic process  neuron projection morphogenesis  regulation of catalytic activity  regulation of sequence-specific DNA binding transcription factor activity  regulation of gastric acid secretion  renal sodium ion absorption  
Ontology : EGO-EBIregulation of cell growth  protein serine/threonine kinase activity  protein serine/threonine kinase activity  protein serine/threonine/tyrosine kinase activity  calcium channel regulator activity  protein binding  ATP binding  nucleus  cytoplasm  mitochondrion  endoplasmic reticulum membrane  cytosol  cytosol  plasma membrane  protein phosphorylation  sodium ion transport  apoptotic process  response to stress  cellular response to DNA damage stimulus  long-term memory  regulation of blood pressure  potassium channel regulator activity  nuclear speck  sodium channel regulator activity  chloride channel regulator activity  peptidyl-serine phosphorylation  regulation of cell migration  positive regulation of transporter activity  ion transmembrane transport  intracellular signal transduction  regulation of cell proliferation  regulation of apoptotic process  neuron projection morphogenesis  regulation of catalytic activity  regulation of sequence-specific DNA binding transcription factor activity  regulation of gastric acid secretion  renal sodium ion absorption  
Pathways : KEGGFoxO signaling pathway    PI3K-Akt signaling pathway    Aldosterone-regulated sodium reabsorption   
REACTOMEO00141 [protein]
REACTOME PathwaysR-HSA-6804757 [pathway]   
NDEx NetworkSGK1
Atlas of Cancer Signalling NetworkSGK1
Wikipedia pathwaysSGK1
Orthology - Evolution
OrthoDB6446
GeneTree (enSembl)ENSG00000118515
Phylogenetic Trees/Animal Genes : TreeFamSGK1
HOVERGENO00141
HOGENOMO00141
Homologs : HomoloGeneSGK1
Homology/Alignments : Family Browser (UCSC)SGK1
Gene fusions - Rearrangements
Fusion : MitelmanFGF13/SGK1 [Xq26.3/6q23.2]  [t(X;6)(q27;q23)]  
Fusion : MitelmanPLP1/SGK1 [Xq22.2/6q23.2]  [t(X;6)(q22;q23)]  
Fusion : MitelmanSLC2A12/SGK1 [6q23.2/6q23.2]  [t(6;6)(q23;q23)]  
Fusion: TCGAPLP1 Xq22.2 SGK1 6q23.2 LGG
Fusion: TCGASLC2A12 6q23.2 SGK1 6q23.2 HNSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSGK1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SGK1
dbVarSGK1
ClinVarSGK1
1000_GenomesSGK1 
Exome Variant ServerSGK1
ExAC (Exome Aggregation Consortium)SGK1 (select the gene name)
Genetic variants : HAPMAP6446
Genomic Variants (DGV)SGK1 [DGVbeta]
DECIPHERSGK1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSGK1 
Mutations
ICGC Data PortalSGK1 
TCGA Data PortalSGK1 
Broad Tumor PortalSGK1
OASIS PortalSGK1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSGK1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSGK1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SGK1
DgiDB (Drug Gene Interaction Database)SGK1
DoCM (Curated mutations)SGK1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SGK1 (select a term)
intoGenSGK1
NCG5 (London)SGK1
Cancer3DSGK1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602958   
Orphanet
MedgenSGK1
Genetic Testing Registry SGK1
NextProtO00141 [Medical]
TSGene6446
GENETestsSGK1
Target ValidationSGK1
Huge Navigator SGK1 [HugePedia]
snp3D : Map Gene to Disease6446
BioCentury BCIQSGK1
ClinGenSGK1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6446
Chemical/Pharm GKB GenePA162403013
Clinical trialSGK1
Miscellaneous
canSAR (ICR)SGK1 (select the gene name)
Probes
Litterature
PubMed222 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSGK1
EVEXSGK1
GoPubMedSGK1
iHOPSGK1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jun 7 12:14:32 CEST 2017

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