Neurochemical Research

, Volume 33, Issue 4, pp 609–613 | Cite as

Dex-ras1 and Serum- and Glucocorticoid-inducible Protein Kinase 1: Regulation of Expression by Dexamethasone in HEK293 Cells

  • Ghassem Attarzadeh-Yazdi
  • Michael J. Shipston
  • Ferenc A. Antoni
Original Paper


The molecular and cellular basis of the psychotropic actions of adrenal corticosteroids is poorly understood. Previously, we reported that modulation of large conductance Ca2+-activated potassium channel (BK-channel) function by glucocorticoids can be recapitulated in human embryonic kidney293 (HEK293) cells (J Physiol 537:57, 2001). In the present paper, we examined the effect of dexamethasone on the expression of candidate mediator proteins of glucocorticoid action, dex-ras1 and serum and glucocorticoid inducible protein kinase 1 (SGK), in HEK293 cells. Dex-ras1 mRNA was readily detectable under basal conditions however, no changes of dex-ras1 mRNA expression occurred upon exposure to 100 nM of dexamethasone for 2 h. In contrast, a 2.5-fold increase of SGK mRNA was found under similar conditions. Total levels of cellular SGK protein were unaltered upon exposure to dexamethasone, but a marked increase of SGK in a Triton-X100 insoluble fraction was observed. BK-channel α-subunits could not be co-immunoprecipitated with SGK. In summary, SGK, but not dex-ras1, mRNA is rapidly induced by glucocorticoid stimulation in HEK293 cells. However, there appears to be no direct protein-protein interaction between SGK and BK-channel α-subunits.


HEK293 Cell Mouse Mammary Tumor Virus NCBI Accession Number AtT20 Cell Glucocorticoid Responsive Gene 
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  1. 1.
    Checkley S (1996) The neuroendocrinology of depression and chronic stress. Br Med Bull 52:597–617PubMedGoogle Scholar
  2. 2.
    de Kloet E, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475PubMedCrossRefGoogle Scholar
  3. 3.
    Dallman MF, Akana SF, Scribner K, Bradbury MJ, Walker C-D, Strack AM, Cascio CS (1992) Stress, feedback and facilitation on the hypothalamo-pituitary-adrenal axis. J Neuroendocrinol 4:517–526CrossRefGoogle Scholar
  4. 4.
    Antoni FA (1996) Calcium checks cyclic AMP—mechanism of corticosteroid feedback in adenohypophysial corticotrophs. J Neuroendocrinol 8:659–672PubMedCrossRefGoogle Scholar
  5. 5.
    Joëls M (1997) Steroid hormones and excitability in the mammalian brain. Front Neuroendocrinol 18:2–48PubMedCrossRefGoogle Scholar
  6. 6.
    Shipston MJ, Kelly JS, Antoni FA (1996) Glucocorticoids block protein kinase A inhibition of calcium-activated potassium channels. J Biol Chem 271:9197–9200PubMedCrossRefGoogle Scholar
  7. 7.
    Tian LJ, Knaus HG, Shipston MJ (1998) Glucocorticoid regulation of calcium-activated potassium channels mediated by serine/threonine protein phosphatase. J Biol Chem 273:13531–13536PubMedCrossRefGoogle Scholar
  8. 8.
    Tian L, Hammond MS, Florance H, Antoni FA, Shipston MJ (2001) Alternative splicing determines sensitivity of murine calcium-activated potassium channels to glucocorticoids. J Physiol (Lond) 537:57–68CrossRefGoogle Scholar
  9. 9.
    Kemppainen RJ, Behrend EN (1998) Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells. J Biol Chem 273:3129–3131PubMedCrossRefGoogle Scholar
  10. 10.
    Kemppainen RJ, Cox E, Behrend EN, Brogan MD, Ammons JM (2003) Identification of a glucocorticoid response element in the 3′-flanking region of the human Dexras1 gene. Biochim Biophys Acta 1627:85–89PubMedGoogle Scholar
  11. 11.
    Graham TE, Key TA, Kilpatrick K, Dorin RI (2001) Dexras1/AGS-1, a steroid hormone-induced guanosine triphosphate-binding protein, inhibits 3′, 5′-cyclic adenosine monophosphate-stimulated secretion in AtT-20 corticotroph cells. Endocrinology 142:2631–2640PubMedCrossRefGoogle Scholar
  12. 12.
    Leckie C, Chapman KE, Edwards CR, Seckl JR (1995) LLC-PK1 cells model 11 beta-hydroxysteroid dehydrogenase type 2 regulation of glucocorticoid access to renal mineralocorticoid receptors. Endocrinology 136:5561–5569PubMedCrossRefGoogle Scholar
  13. 13.
    Shipston MJ, Duncan RR, Clark AG, Antoni FA, Tian L (1999) Molecular components of large conductance calcium activated potassium (BK) channels in mouse pituitary corticotropes. Mol Endocrinol 13:1728–1737PubMedCrossRefGoogle Scholar
  14. 14.
    Antoni FA, Palkovits M, Simpson J, Smith SM, Leitch AL, Rosie R, Fink G, Paterson JM (1998) Ca2+/calcineurin-inhibited adenylyl cyclase highly abundant in forebrain regions important for learning and memory. J Neurosci 18:9650–9661PubMedGoogle Scholar
  15. 15.
    Graham TE, Qiao Z, Dorin RI (2004) Dexras1 inhibits adenylyl cyclase. Biochem Biophys Res Commun 316:307–312PubMedCrossRefGoogle Scholar
  16. 16.
    Cismowski MJ, Takesono A, Ma C, Lizano JS, Xie X, Fuernkranz H, Lanier SM, Duzic E (1999) Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling. Nat Biotechnol 17:878–883PubMedCrossRefGoogle Scholar
  17. 17.
    Meijer O, Williamson A, Dallman M, Pearce D (2000) Transcriptional repression of the 5-HT1A receptor promoter by corticosterone via mineralocorticoid receptors depends on the cellular context. J Neuroendocrinol 12:245–254PubMedCrossRefGoogle Scholar
  18. 18.
    Pearce D (2001) The role of SGK1 in hormone-regulated sodium transport. Trends Endocrinol Metab 12:341–347PubMedCrossRefGoogle Scholar
  19. 19.
    Alvarez de la Rosa D, Coric T, Todorovic N, Shao D, Wang T, Canessa CM (2003) Distribution and regulation of expression of serum- and glucocorticoid-induced kinase-1 in the rat kidney. J Physiol 551:455–466CrossRefGoogle Scholar
  20. 20.
    Brickley DR, Mikosz CA, Hagan CR, Conzen SD (2002) Ubiquitin modification of serum and glucocorticoid-induced protein kinase-1 (SGK-1). J Biol Chem 277:43064–43070PubMedCrossRefGoogle Scholar
  21. 21.
    Engelsberg A, Kobelt F, Kuhl D (2006) The N-terminus of the serum- and glucocorticoid-inducible kinase Sgk1 specifies mitochondrial localization and rapid turnover. Biochem J 399:69–76PubMedCrossRefGoogle Scholar
  22. 22.
    Brown DA (2006) Lipid rafts, detergent-resistant membranes, and raft targeting signals. Physiology (Bethesda) 21:430–439Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Ghassem Attarzadeh-Yazdi
    • 1
  • Michael J. Shipston
    • 1
  • Ferenc A. Antoni
    • 1
  1. 1.Membrane Biology Group, Centre for Integrative PhysiologyUniversity of EdinburghEdinburghUK

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