Serum- and Glucocorticoid-inducible Kinase 1 and the Response to Cell Stress

Overview

Journal Cell Stress

Date 2019 Jun 22

PMID 31225494

Citations 31

Authors

Florian Lang

Christos Stournaras

Nefeli Zacharopoulou

Jakob Voelkl

Ioana Alesutan

Affiliations

Soon will be listed here.

Abstract

Expression of the serum- and glucocorticoid-inducible kinase 1 (SGK1) is up-regulated by several types of cell stress, such as ischemia, radiation and hyperosmotic shock. The SGK1 protein is activated by a signaling cascade involving phosphatidylinositide-3-kinase (PI3K), 3-phosphoinositide-dependent kinase 1 (PDK1) and mammalian target of rapamycin (mTOR). SGK1 up-regulates Na/K-ATPase, a variety of carriers including Na-,K-,2Cl- cotransporter (NKCC), NaCl cotransporter (NCC), Na/H exchangers, diverse amino acid transporters and several glucose carriers such as Na-coupled glucose transporter SGLT1. SGK1 further up-regulates a large number of ion channels including epithelial Na channel ENaC, voltagegated Na channel SCN5A, Ca release-activated Ca channel (ORAI1) with its stimulator STIM1, epithelial Ca channels TRPV5 and TRPV6 and diverse K channels. Furthermore, SGK1 influences transcription factors such as nuclear factor kappa-B (NF-κB), p53 tumor suppressor protein, cAMP responsive element-binding protein (CREB), activator protein-1 (AP-1) and forkhead box O3 protein (FOXO3a). Thus, SGK1 supports cellular glucose uptake and glycolysis, angiogenesis, cell survival, cell migration, and wound healing. Presumably as last line of defense against tissue injury, SGK1 fosters tissue fibrosis and tissue calcification replacing energy consuming cells.

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References

Waldegger S, Klingel K, Barth P, Sauter M, Rfer M, Kandolf R . h-sgk serine-threonine protein kinase gene as transcriptional target of transforming growth factor beta in human intestine. Gastroenterology. 1999; 116(5):1081-8. DOI: 10.1016/s0016-5085(99)70011-9. View

Park J, Leong M, Buse P, Maiyar A, Firestone G, Hemmings B . Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J. 1999; 18(11):3024-33. PMC: 1171384. DOI: 10.1093/emboj/18.11.3024. View

Firestone G, Giampaolo J, OKeeffe B . Stimulus-dependent regulation of serum and glucocorticoid inducible protein kinase (SGK) transcription, subcellular localization and enzymatic activity. Cell Physiol Biochem. 2003; 13(1):1-12. DOI: 10.1159/000070244. View

Artunc F, Amann K, Nasir O, Friedrich B, Sandulache D, Jahovic N . Blunted DOCA/high salt induced albuminuria and renal tubulointerstitial damage in gene-targeted mice lacking SGK1. J Mol Med (Berl). 2006; 84(9):737-46. DOI: 10.1007/s00109-006-0082-0. View

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(4):1151-78. DOI: 10.1152/physrev.00050.2005. View

Terada Y, Kuwana H, Kobayashi T, Okado T, Suzuki N, Yoshimoto T . Aldosterone-stimulated SGK1 activity mediates profibrotic signaling in the mesangium. J Am Soc Nephrol. 2008; 19(2):298-309. PMC: 2396734. DOI: 10.1681/ASN.2007050531. View

Dehner M, Hadjihannas M, Weiske J, Huber O, Behrens J . Wnt signaling inhibits Forkhead box O3a-induced transcription and apoptosis through up-regulation of serum- and glucocorticoid-inducible kinase 1. J Biol Chem. 2008; 283(28):19201-10. DOI: 10.1074/jbc.M710366200. View

Peterson T, Laplante M, Thoreen C, Sancak Y, Kang S, Kuehl W . DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009; 137(5):873-86. PMC: 2758791. DOI: 10.1016/j.cell.2009.03.046. View

Lang F, Artunc F, Vallon V . The physiological impact of the serum and glucocorticoid-inducible kinase SGK1. Curr Opin Nephrol Hypertens. 2009; 18(5):439-48. PMC: 2883450. DOI: 10.1097/MNH.0b013e32832f125e. View

10.

Dibble C, Asara J, Manning B . Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol. 2009; 29(21):5657-70. PMC: 2772744. DOI: 10.1128/MCB.00735-09. View

11.

Rosner M, Dolznig H, Fuchs C, Siegel N, Valli A, Hengstschlager M . CDKs as therapeutic targets for the human genetic disease tuberous sclerosis?. Eur J Clin Invest. 2009; 39(12):1033-5. DOI: 10.1111/j.1365-2362.2009.02213.x. View

12.

Lang F, Gorlach A, Vallon V . Targeting SGK1 in diabetes. Expert Opin Ther Targets. 2009; 13(11):1303-11. PMC: 2798808. DOI: 10.1517/14728220903260807. View

13.

Treins C, Warne P, Magnuson M, Pende M, Downward J . Rictor is a novel target of p70 S6 kinase-1. Oncogene. 2009; 29(7):1003-16. DOI: 10.1038/onc.2009.401. View

14.

Rusai K, Prokai A, Szebeni B, Fekete A, Treszl A, Vannay A . Role of serum and glucocorticoid-regulated kinase-1 in the protective effects of erythropoietin during renal ischemia/reperfusion injury. Biochem Pharmacol. 2009; 79(8):1173-81. DOI: 10.1016/j.bcp.2009.11.022. View

15.

Szebeni B, Vannay A, Sziksz E, Prokai A, Cseh A, Veres G . Increased expression of serum- and glucocorticoid-regulated kinase-1 in the duodenal mucosa of children with coeliac disease. J Pediatr Gastroenterol Nutr. 2009; 50(2):147-53. DOI: 10.1097/MPG.0b013e3181b47608. View

16.

Lang F, Gorlach A . Heterocyclic indazole derivatives as SGK1 inhibitors, WO2008138448. Expert Opin Ther Pat. 2009; 20(1):129-35. DOI: 10.1517/13543770903365209. View

17.

Murakami Y, Hosoi F, Izumi H, Maruyama Y, Ureshino H, Watari K . Identification of sites subjected to serine/threonine phosphorylation by SGK1 affecting N-myc downstream-regulated gene 1 (NDRG1)/Cap43-dependent suppression of angiogenic CXC chemokine expression in human pancreatic cancer cells. Biochem Biophys Res Commun. 2010; 396(2):376-81. DOI: 10.1016/j.bbrc.2010.04.100. View

18.

Lyo D, Xu L, Foster D . Phospholipase D stabilizes HDM2 through an mTORC2/SGK1 pathway. Biochem Biophys Res Commun. 2010; 396(2):562-5. PMC: 3010228. DOI: 10.1016/j.bbrc.2010.04.148. View

19.

Heise C, Xu B, Deaton S, Cha S, Cheng C, Earnest S . Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members. J Biol Chem. 2010; 285(33):25161-7. PMC: 2919078. DOI: 10.1074/jbc.M110.103432. View

20.

Lang F, Perrotti N, Stournaras C . Colorectal carcinoma cells--regulation of survival and growth by SGK1. Int J Biochem Cell Biol. 2010; 42(10):1571-5. DOI: 10.1016/j.biocel.2010.05.016. View