Serum- and glucocorticoid-inducible kinase 1 and the response to cell stress

Authors:

Florian Lang1, Christos Stournaras2, Nefeli Zacharopoulou2, Jakob Voelkl3,4, Ioana Alesutan3,4,5
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Affiliations:

1 Department of Vegetative and Clinical Physiology, Eberhard-Karls-University, Tübingen, Germany.

2 Department of Biochemistry, University of Crete Medical School, Voutes, Heraklion, Greece-

3 Department of Internal Medicine and Cardiology, Charité – Universitätsmedizin Berlin, Germany.

4 DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany.

5 Berlin Institute of Health (BIH), Berlin, Germany.

Keywords: 

SGK1, glycolysis, cell survival, cell migration, angiogenesis, fibrosis and tissue calcification.

Abbreviations:

mTOR – mammalian target of rapamycin,

NF-κB- nuclear factor-kappa B,

SGK1 – serum- and glucocorticoid-inducible kinase 1,

TGFβ – transforming growth factor beta,

VSMC – vascular smooth muscle cell.

Corresponding Author(s):

Florian Lang, MD, Department of Physiology, University of Tübingen, Wilhelmstr. 56, 72076 Tübingen, Germany; Phone +49-7071 29 72194; Fax: +49-7071 29 5618 florian.lang@uni-tuebingen.de

Conflict of interest statement:

The authors declare that they have no conflict of interest.

Please cite this article as:

Florian Lang, Christos Stournaras, Nefeli Zacharopoulou, Jakob Voelkl, Ioana Alesutan (2018). Serum- and glucocorticoid-inducible kinase 1 and the response to cell stress. Cell Stress 3(1): 1-8. doi: 10.15698/cst2019.01.170

© 2019 Lang et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

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, voltage-gated Na+ channel SCN5A, Ca2+ release-activated Ca2+ channel (ORAI1) with its stimulator STIM1, epithelial Ca2+ 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.