Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

SGK-1 (Serum- and Glucocorticoid-Inducible Kinase-1)

  • David Della-MorteEmail author
  • Donatella Pastore
  • Barbara Capuani
  • Francesca Pacifici
  • Davide Lauro
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101807


Historical Background

The serum- and glucocorticoid-inducible kinase-1 (SGK-1) was originally cloned in 1993 by Webster et al., as an immediate early gene transcriptionally stimulated by serum and glucocorticoids in rat mammary tumor cells (Webster et al. 1993a, b). Few years later, the human isoform was cloned and characterized as a putative serine/threonine protein kinase transcriptionally modified during alterations of cell volume in human hepatoma cell line (Waldegger et al. 1997). The gene encoding human SGK-1 was localized to chromosome 6q23 (Waldegger et al. 1998). Subsequently were identified two novel isoforms homologous of SGK-1, the SGK-2 and SGK-3, that share 80% amino acid sequence identity in their catalytic domain with SGK-1 (Kobayashi et al. 1999). SGK kinases are expressed in a wide variety of species such as Caenorhabditis elegans and yeast that express two orthologs, Ypk1 and Ypk2 (Lauro et al. 2015). In...

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  1. Fejes-Toth G, Frindt G, Naray-Fejes-Toth A, Palmer LG. Epithelial Na+ channel activation and processing in mice lacking SGK1. Am J Physiol Renal Physiol. 2008;294:F1298–305. doi:10.1152/ajprenal.00579.2007.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ferrelli F, Pastore D, Capuani B, Lombardo MF, Blot-Chabaud M, Coppola A, et al. Serum glucocorticoid inducible kinase (SGK)-1 protects endothelial cells against oxidative stress and apoptosis induced by hyperglycaemia. Acta Diabetol. 2015;52:55–64. doi:10.1007/s00592-014-0600-4.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Firestone GL, Giampaolo JR, O'Keeffe BA. Stimulus-dependent regulation of serum and glucocorticoid inducible protein kinase (SGK) transcription, subcellular localization and enzymatic activity. Cell Physiol Biochem. 2003;13:1–12.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Kobayashi T, Deak M, Morrice N, Cohen P. Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem J. 1999;344(Pt 1):189–97.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Lang F, Bohmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V. (Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms. Physiol Rev. 2006;86:1151–78. doi:10.1152/physrev.00050.2005.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Lang F, Gorlach A, Vallon V. Targeting SGK1 in diabetes. Expert Opin Ther Targets. 2009;13:1303–11. doi:10.1517/14728220903260807.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Lauro D, Pastore D, Capuani B, Pacifici F, Palmirotta R, Abete P, et al. Role of serum and glucocorticoid-inducible kinase (SGK)-1 in senescence: a novel molecular target against age-related diseases. Curr Med Chem. 2015;22:3765–88.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Leong ML, Maiyar AC, Kim B, O'Keeffe BA, Firestone GL. Expression of the serum- and glucocorticoid-inducible protein kinase, Sgk, is a cell survival response to multiple types of environmental stress stimuli in mammary epithelial cells. J Biol Chem. 2003;278:5871–82. doi:10.1074/jbc.M211649200.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Liu H, Yu J, Xia T, Xiao Y, Zhang Q, Liu B, et al. Hepatic serum- and glucocorticoid-regulated protein kinase 1 (SGK1) regulates insulin sensitivity in mice via extracellular-signal-regulated kinase 1/2 (ERK1/2). Biochem J. 2014;464:281–9. doi:10.1042/BJ20141005.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Mikosz CA, Brickley DR, Sharkey MS, Moran TW, Conzen SD. Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1. J Biol Chem. 2001;276:16649–54. doi:10.1074/jbc.M010842200.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Nasir O, Wang K, Foller M, Gu S, Bhandaru M, Ackermann TF, et al. Relative resistance of SGK1 knockout mice against chemical carcinogenesis. IUBMB Life. 2009;61:768–76. doi:10.1002/iub.209.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Pastore D, Della-Morte D, Coppola A, Capuani B, Lombardo MF, Pacifici F, et al. SGK-1 protects kidney cells against apoptosis induced by ceramide and TNF-alpha. Cell Death Dis. 2015;6:e1890. doi:10.1038/cddis.2015.232.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Rangone H, Poizat G, Troncoso J, Ross CA, MacDonald ME, Saudou F, et al. The serum- and glucocorticoid-induced kinase SGK inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin. Eur J Neurosci. 2004;19:273–9.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Sahin P, McCaig C, Jeevahan J, Murray JT, Hainsworth AH. The cell survival kinase SGK1 and its targets FOXO3a and NDRG1 in aged human brain. Neuropathol Appl Neurobiol. 2013;39:623–33. doi:10.1111/nan.12023.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Schoenebeck B, Bader V, Zhu XR, Schmitz B, Lubbert H, Stichel CC. Sgk1, a cell survival response in neurodegenerative diseases. Mol Cell Neurosci. 2005;30:249–64. doi:10.1016/j.mcn.2005.07.017.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Schwab M, Lupescu A, Mota M, Mota E, Frey A, Simon P, et al. Association of SGK1 gene polymorphisms with type 2 diabetes. Cell Physiol Biochem. 2008;21:151–60. doi:10.1159/000113757.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49:355–64. doi:10.1161/01.HYP.0000255636.11931.a2.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Ullrich S, Berchtold S, Ranta F, Seebohm G, Henke G, Lupescu A, et al. Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates glucocorticoid-induced inhibition of insulin secretion. Diabetes. 2005;54:1090–9.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Waldegger S, Barth P, Raber G, Lang F. Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume. Proc Natl Acad Sci U S A. 1997;94:4440–5.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Waldegger S, Erdel M, Nagl UO, Barth P, Raber G, Steuer S, et al. Genomic organization and chromosomal localization of the human SGK protein kinase gene. Genomics. 1998;51:299–302. doi:10.1006/geno.1998.5258.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Webster MK, Goya L, Firestone GL. Immediate-early transcriptional regulation and rapid mRNA turnover of a putative serine/threonine protein kinase. J Biol Chem. 1993a;268:11482–5.PubMedPubMedCentralGoogle Scholar
  22. Webster MK, Goya L, Ge Y, Maiyar AC, Firestone GL. Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol Cell Biol. 1993b;13:2031–40.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Zhang W, Xia X, Reisenauer MR, Rieg T, Lang F, Kuhl D, et al. Aldosterone-induced Sgk1 relieves Dot1a-Af9-mediated transcriptional repression of epithelial Na+ channel alpha. J Clin Invest. 2007;117:773–83. doi:10.1172/JCI29850.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • David Della-Morte
    • 1
    • 2
    Email author
  • Donatella Pastore
    • 1
  • Barbara Capuani
    • 1
  • Francesca Pacifici
    • 1
  • Davide Lauro
    • 1
  1. 1.Department of Systems Medicine, School of MedicineUniversity of Rome Tor VergataRomeItaly
  2. 2.IRCCS San Raffaele PisanaRomeItaly