The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

SGK1  -  serum/glucocorticoid regulated kinase 1

Homo sapiens

Synonyms: SGK, Serine/threonine-protein kinase Sgk1, Serum/glucocorticoid-regulated kinase 1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of SGK


High impact information on SGK

  • Absorption of NaCl is a rather steady process that is controlled by steroid hormones regulating the expression of epithelial Na(+) channels (ENaC), the Na(+)-K(+)-ATPase, and additional modulating factors such as the serum- and glucocorticoid-regulated kinase SGK [5].
  • Consistent with this, an activated form of CISK but not of the related kinase SGK1 phosphorylates specific sites of AIP4 in vitro [6].
  • Thus, the hydrophobic motif phosphorylation of S6K and SGK converts them into substrates that can be activated by PDK1 [7].
  • PKB/Akt and serum and glucocorticoid-regulated kinase (SGK) family kinases are important downstream targets of phosphatidylinositol 3 (PI-3) kinase and have been shown to mediate a variety of cellular processes, including cell growth and survival [8].
  • Although regulation of Akt can be achieved through several mechanisms, including its phosphoinositide-binding Pleckstrin homology (PH) domain, how SGK kinases are targeted and regulated remains to be elucidated [8].

Chemical compound and disease context of SGK


Biological context of SGK

  • These findings indicate that SGK acts in concert with Akt to propagate the effects of PI3K activation within the nucleus and to mediate the biological outputs of PI3K signaling, including cell survival and cell cycle progression [13].
  • Consistent with these findings, the Ser422Asp mutant of SGK is activated by phosphorylation (probably at Thr256) in unstimulated 293 cells, and activation is unaffected by inhibitors of PtdIns 3-kinase [14].
  • Opposite shifts of gating properties were elicited by mutation of serine to alanine (S483ASCN5A and S663ASCN5A) in the SGK consensus sequences of SCN5A [15].
  • The in vivo physiological significance of SGK dependent regulation of the other channels remains to be shown even though circumstantial evidence points to involvement in the regulation of epithelial transport, cell volume, cell proliferation, cardiac action potential and neuroexcitability [16].
  • The substrate specificity of SGK isoforms superficially resembles that of PKB in that serine and threonine residues lying in Arg-Xaa-Arg-Xaa-Xaa-Ser/Thr sequences (where Xaa is a variable amino acid) are phosphorylated [17].

Anatomical context of SGK


Associations of SGK with chemical compounds

  • Similar to glutamate-induced currents, [3H] glutamate uptake and cell surface abundance of the transporter were increased by the SGK isoforms and down-regulated by the ubiquitin ligase Nedd4-2 [18].
  • The activation of SGK by PDK1 in vitro is unaffected by PtdIns(3,4,5)P3, abolished by the mutation of Ser422 to Ala, and greatly potentiated by mutation of Ser422 to Asp (although this mutation does not activate SGK itself) [14].
  • This study determined the expression and functional role of SGK-1 in PTCs in high glucose conditions [2].
  • SGK-1 overexpression increased PTC growth (P < 0.0001), progression through the cell cycle (P < 0.001), and increased NHE3 mRNA (P < 0.01), which were all reversed with PKI166 [2].
  • Regulation of sodium transport in mammalian collecting duct cells by aldosterone-induced kinase, SGK1: structure/function studies [22].
  • An endogenous stimulus of SGK1, insulin, increased IKKalpha and NF-kappaB phosphorylation as well as NF-kappaB acetylation and NF-kappaB activity, but SGK1 small interfering RNA transfection blocked these effects of insulin [23].

Physical interactions of SGK

  • Pull down assays reveal that SGK1 interacts with NHERF2 through the second PDZ domain of NHERF2 [24].
  • Consistent with this model, we found that SGK bound to hNedd4-2 and hNedd4 [25].
  • Here, we report the identification of serum and glucocorticoid-inducible kinase (SGK) as a cellular protein that physically interacts with BMK1 [26].

Enzymatic interactions of SGK


Regulatory relationships of SGK

  • SGK1 kinase upregulates GLUT1 activity and plasma membrane expression [30].
  • SCN5A currents were activated by coexpression of either wild-type SGK1 or SGK3 or the constitutively active S422DSGK1 [15].
  • Replacement of serine by alanine at the two SGK consensus sites decreased I(HERG) but neither mutation abolished the stimulating effect of SGK3 [31].
  • The present study aims to explore whether TRPV5 is regulated by the serum and glucocorticoid inducible kinase SGK1, a kinase transcriptionally upregulated by 1,25(OH) 2D3 [32].
  • HERG was expressed in Xenopus oocytes with or without additional expression of SGK1 or SGK3 [31].
  • Infection of primary hepatocytes with an adenoviral vector encoding SGK1 enhanced the ERK phosphorylation under serum-starved conditions and this was blocked by the expression of kinase-dead SGK1 [33].

Other interactions of SGK


Analytical, diagnostic and therapeutic context of SGK


  1. (Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms. Lang, F., B??hmer, C., Palmada, M., Seebohm, G., Strutz-Seebohm, N., Vallon, V. Physiol. Rev. (2006) [Pubmed]
  2. High glucose transactivates the EGF receptor and up-regulates serum glucocorticoid kinase in the proximal tubule. Saad, S., Stevens, V.A., Wassef, L., Poronnik, P., Kelly, D.J., Gilbert, R.E., Pollock, C.A. Kidney Int. (2005) [Pubmed]
  3. Regulation of glucose transporter SGLT1 by ubiquitin ligase Nedd4-2 and kinases SGK1, SGK3, and PKB. Dieter, M., Palmada, M., Rajamanickam, J., Aydin, A., Busjahn, A., Boehmer, C., Luft, F.C., Lang, F. Obes. Res. (2004) [Pubmed]
  4. Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Boehmer, C., Rajamanickam, J., Schniepp, R., Kohler, K., Wulff, P., Kuhl, D., Palmada, M., Lang, F. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  5. Electrolyte transport in the mammalian colon: mechanisms and implications for disease. Kunzelmann, K., Mall, M. Physiol. Rev. (2002) [Pubmed]
  6. CISK attenuates degradation of the chemokine receptor CXCR4 via the ubiquitin ligase AIP4. Slagsvold, T., Marchese, A., Brech, A., Stenmark, H. EMBO J. (2006) [Pubmed]
  7. The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB. Biondi, R.M., Kieloch, A., Currie, R.A., Deak, M., Alessi, D.R. EMBO J. (2001) [Pubmed]
  8. Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides. Xu, J., Liu, D., Gill, G., Songyang, Z. J. Cell Biol. (2001) [Pubmed]
  9. The serum- and glucocorticoid-induced kinase SGK inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin. Rangone, H., Poizat, G., Troncoso, J., Ross, C.A., MacDonald, M.E., Saudou, F., Humbert, S. Eur. J. Neurosci. (2004) [Pubmed]
  10. Sgk1, a cell survival response in neurodegenerative diseases. Schoenebeck, B., Bader, V., Zhu, X.R., Schmitz, B., Lübbert, H., Stichel, C.C. Mol. Cell. Neurosci. (2005) [Pubmed]
  11. DOCA-induced phosphorylation of glycogen synthase kinase 3beta. Wyatt, A.W., Hussain, A., Amann, K., Klingel, K., Kandolf, R., Artunc, F., Grahammer, F., Huang, D.Y., Vallon, V., Kuhl, D., Lang, F. Cell. Physiol. Biochem. (2006) [Pubmed]
  12. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors. Nagase, M., Yoshida, S., Shibata, S., Nagase, T., Gotoda, T., Ando, K., Fujita, T. J. Am. Soc. Nephrol. (2006) [Pubmed]
  13. Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Brunet, A., Park, J., Tran, H., Hu, L.S., Hemmings, B.A., Greenberg, M.E. Mol. Cell. Biol. (2001) [Pubmed]
  14. 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) [Pubmed]
  15. Serum and glucocorticoid inducible kinases in the regulation of the cardiac sodium channel SCN5A. Boehmer, C., Wilhelm, V., Palmada, M., Wallisch, S., Henke, G., Brinkmeier, H., Cohen, P., Pieske, B., Lang, F. Cardiovasc. Res. (2003) [Pubmed]
  16. Regulation of channels by the serum and glucocorticoid-inducible kinase - implications for transport, excitability and cell proliferation. Lang, F., Henke, G., Embark, H.M., Waldegger, S., Palmada, M., Böhmer, C., Vallon, V. Cell. Physiol. Biochem. (2003) [Pubmed]
  17. Regulation and physiological roles of serum- and glucocorticoid-induced protein kinase isoforms. Lang, F., Cohen, P. Sci. STKE (2001) [Pubmed]
  18. Post-translational regulation of EAAT2 function by co-expressed ubiquitin ligase Nedd4-2 is impacted by SGK kinases. Boehmer, C., Palmada, M., Rajamanickam, J., Schniepp, R., Amara, S., Lang, F. J. Neurochem. (2006) [Pubmed]
  19. K+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK. Gamper, N., Fillon, S., Feng, Y., Friedrich, B., Lang, P.A., Henke, G., Huber, S.M., Kobayashi, T., Cohen, P., Lang, F. Pflugers Arch. (2002) [Pubmed]
  20. Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Kobayashi, T., Deak, M., Morrice, N., Cohen, P. Biochem. J. (1999) [Pubmed]
  21. Regulation of intestinal phosphate cotransporter NaPi IIb by ubiquitin ligase Nedd4-2 and by serum- and glucocorticoid-dependent kinase 1. Palmada, M., Dieter, M., Speil, A., Böhmer, C., Mack, A.F., Wagner, H.J., Klingel, K., Kandolf, R., Murer, H., Biber, J., Closs, E.I., Lang, F. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  22. Regulation of sodium transport in mammalian collecting duct cells by aldosterone-induced kinase, SGK1: structure/function studies. Náray-Fejes-Tóth, A., Helms, M.N., Stokes, J.B., Fejes-Tóth, G. Mol. Cell. Endocrinol. (2004) [Pubmed]
  23. 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, D.J., Su, C.C., Ma, Y.L., Lee, E.H. J. Biol. Chem. (2009) [Pubmed]
  24. Molecular requirements for the regulation of the renal outer medullary K(+) channel ROMK1 by the serum- and glucocorticoid-inducible kinase SGK1. Palmada, M., Embark, H.M., Yun, C., Böhmer, C., Lang, F. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  25. Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. Snyder, P.M., Olson, D.R., Thomas, B.C. J. Biol. Chem. (2002) [Pubmed]
  26. BMK1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinase. Hayashi, M., Tapping, R.I., Chao, T.H., Lo, J.F., King, C.C., Yang, Y., Lee, J.D. J. Biol. Chem. (2001) [Pubmed]
  27. Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Murray, J.T., Campbell, D.G., Morrice, N., Auld, G.C., Shpiro, N., Marquez, R., Peggie, M., Bain, J., Bloomberg, G.B., Grahammer, F., Lang, F., Wulff, P., Kuhl, D., Cohen, P. Biochem. J. (2004) [Pubmed]
  28. Serum and glucocorticoid-regulated kinase Sgk1 inhibits insulin-dependent activation of phosphomannomutase 2 in transfected COS-7 cells. Menniti, M., Iuliano, R., Amato, R., Boito, R., Corea, M., Le Pera, I., Gulletta, E., Fuiano, G., Perrotti, N. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  29. Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradation. Zhou, R., Snyder, P.M. J. Biol. Chem. (2005) [Pubmed]
  30. SGK1 kinase upregulates GLUT1 activity and plasma membrane expression. Palmada, M., Boehmer, C., Akel, A., Rajamanickam, J., Jeyaraj, S., Keller, K., Lang, F. Diabetes (2006) [Pubmed]
  31. Upregulation of HERG Channels by the Serum and Glucocorticoid Inducible Kinase Isoform SGK3. Maier, G., Palmada, M., Rajamanickam, J., Shumilina, E., Bohmer, C., Lang, F. Cell. Physiol. Biochem. (2006) [Pubmed]
  32. Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in Xenopus oocytes. Embark, H.M., Setiawan, I., Poppendieck, S., van de Graaf, S.F., Boehmer, C., Palmada, M., Wieder, T., Gerstberger, R., Cohen, P., Yun, C.C., Bindels, R.J., Lang, F. Cell. Physiol. Biochem. (2004) [Pubmed]
  33. 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, K.A., Byun, H.S., Kim, Y.R., Choi, B.L., Hong, J.H., Park, J., Seok, J.H., Lee, Y.H., Cho, C.H., Song, I.S., Kim, Y.K., Shen, H.M., Hur, G.M. J. Hepatol. (2009) [Pubmed]
  34. Molecular basis for the substrate specificity of NIMA-related kinase-6 (NEK6). Evidence that NEK6 does not phosphorylate the hydrophobic motif of ribosomal S6 protein kinase and serum- and glucocorticoid-induced protein kinase in vivo. Lizcano, J.M., Deak, M., Morrice, N., Kieloch, A., Hastie, C.J., Dong, L., Schutkowski, M., Reimer, U., Alessi, D.R. J. Biol. Chem. (2002) [Pubmed]
  35. Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3 and protein kinase B. Boehmer, C., Henke, G., Schniepp, R., Palmada, M., Rothstein, J.D., Bröer, S., Lang, F. J. Neurochem. (2003) [Pubmed]
  36. New insights into the role of serum- and glucocorticoid-inducible kinase SGK1 in the regulation of renal function and blood pressure. Vallon, V., Lang, F. Curr. Opin. Nephrol. Hypertens. (2005) [Pubmed]
  37. PPARgamma activation enhances cell surface ENaCalpha via up-regulation of SGK1 in human collecting duct cells. Hong, G., Lockhart, A., Davis, B., Rahmoune, H., Baker, S., Ye, L., Thompson, P., Shou, Y., O'Shaughnessy, K., Ronco, P., Brown, J. FASEB J. (2003) [Pubmed]
  38. Genomic organization and chromosomal localization of the human SGK protein kinase gene. Waldegger, S., Erdel, M., Nagl, U.O., Barth, P., Raber, G., Steuer, S., Utermann, G., Paulmichl, M., Lang, F. Genomics (1998) [Pubmed]
WikiGenes - Universities