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

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Abstract

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.

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References

  1. Checkley S (1996) The neuroendocrinology of depression and chronic stress. Br Med Bull 52:597–617

    PubMed  CAS  Google Scholar 

  2. de Kloet E, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475

    Article  PubMed  Google Scholar 

  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 4:517–526

    Article  CAS  Google Scholar 

  4. Antoni FA (1996) Calcium checks cyclic AMP—mechanism of corticosteroid feedback in adenohypophysial corticotrophs. J Neuroendocrinol 8:659–672

    Article  PubMed  CAS  Google Scholar 

  5. Joëls M (1997) Steroid hormones and excitability in the mammalian brain. Front Neuroendocrinol 18:2–48

    Article  PubMed  Google Scholar 

  6. Shipston MJ, Kelly JS, Antoni FA (1996) Glucocorticoids block protein kinase A inhibition of calcium-activated potassium channels. J Biol Chem 271:9197–9200

    Article  PubMed  CAS  Google Scholar 

  7. Tian LJ, Knaus HG, Shipston MJ (1998) Glucocorticoid regulation of calcium-activated potassium channels mediated by serine/threonine protein phosphatase. J Biol Chem 273:13531–13536

    Article  PubMed  CAS  Google Scholar 

  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) 537:57–68

    Article  CAS  Google Scholar 

  9. Kemppainen RJ, Behrend EN (1998) Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells. J Biol Chem 273:3129–3131

    Article  PubMed  CAS  Google Scholar 

  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 1627:85–89

    PubMed  CAS  Google Scholar 

  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 142:2631–2640

    Article  PubMed  CAS  Google Scholar 

  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 136:5561–5569

    Article  PubMed  CAS  Google Scholar 

  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 13:1728–1737

    Article  PubMed  CAS  Google Scholar 

  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 18:9650–9661

    PubMed  CAS  Google Scholar 

  15. Graham TE, Qiao Z, Dorin RI (2004) Dexras1 inhibits adenylyl cyclase. Biochem Biophys Res Commun 316:307–312

    Article  PubMed  CAS  Google Scholar 

  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 17:878–883

    Article  PubMed  CAS  Google Scholar 

  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 12:245–254

    Article  PubMed  CAS  Google Scholar 

  18. Pearce D (2001) The role of SGK1 in hormone-regulated sodium transport. Trends Endocrinol Metab 12:341–347

    Article  PubMed  CAS  Google Scholar 

  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 551:455–466

    Article  Google Scholar 

  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 277:43064–43070

    Article  PubMed  CAS  Google Scholar 

  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 399:69–76

    Article  PubMed  CAS  Google Scholar 

  22. Brown DA (2006) Lipid rafts, detergent-resistant membranes, and raft targeting signals. Physiology (Bethesda) 21:430–439

    CAS  Google Scholar 

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Correspondence to Ghassem Attarzadeh-Yazdi.

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Special issue article in honor of George Fink.

Presented to mark the 70th birthday of Professor George Fink.

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Attarzadeh-Yazdi, G., Shipston, M.J. & Antoni, F.A. Dex-ras1 and Serum- and Glucocorticoid-inducible Protein Kinase 1: Regulation of Expression by Dexamethasone in HEK293 Cells. Neurochem Res 33, 609–613 (2008). https://doi.org/10.1007/s11064-007-9516-5

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