(Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms
Abstract
The serum- and glucocorticoid-inducible kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress (including cell shrinkage) and hormones (including gluco- and mineralocorticoids). Similar to its isoforms SGK2 and SGK3, SGK1 is activated by insulin and growth factors via phosphatidylinositol 3-kinase and the 3-phosphoinositide-dependent kinase PDK1. SGKs activate ion channels (e.g., ENaC, TRPV5, ROMK, Kv1.3, KCNE1/KCNQ1, GluR1, GluR6), carriers (e.g., NHE3, GLUT1, SGLT1, EAAT1–5), and the Na + -K + -ATPase. They regulate the activity of enzymes (e.g., glycogen synthase kinase-3, ubiquitin ligase Nedd4–2, phosphomannose mutase-2) and transcription factors (e.g., forkhead transcription factor FKHRL1, β-catenin, nuclear factor κB). SGKs participate in the regulation of transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. SGK1 contributes to Na + retention and K + elimination of the kidney, mineralocorticoid stimulation of salt appetite, glucocorticoid stimulation of intestinal Na + /H + exchanger and nutrient transport, insulin-dependent salt sensitivity of blood pressure and salt sensitivity of peripheral glucose uptake, memory consolidation, and cardiac repolarization. A common (∼5% prevalence) SGK1 gene variant is associated with increased blood pressure and body weight. SGK1 may thus contribute to metabolic syndrome. SGK1 may further participate in tumor growth, neurodegeneration, fibrosing disease, and the sequelae of ischemia. SGK3 is required for adequate hair growth and maintenance of intestinal nutrient transport and influences locomotive behavior. In conclusion, the SGKs cover a wide variety of physiological functions and may play an active role in a multitude of pathophysiological conditions. There is little doubt that further targets will be identified that are modulated by the SGK isoforms and that further SGK-dependent in vivo physiological functions and pathophysiological conditions will be defined.
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SGK1 is an immediate early gene induced by a variety of cellular stress.
“SGK1 is an immediate early gene induced by a variety of cellular stress [16].”
From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [16]
SGK1 phosphorylates many substrates in different types of cells.
“SGK1 phosphorylates many substrates in different types of cells [16].”
From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [16]
SGK1 transcription is controlled by a wide variety of additional hormones and further regulators.
“SGK1 transcription is controlled by a wide variety of additional hormones and further regulators including increase of cytosolic Ca 2+ activity and NO (Lang et al. 2006(Lang et al. , 2009)).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 is ubiquitously expressed.
“SGK1 is ubiquitously expressed (Lang et al. 2006(Lang et al. , 2009)).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 is genomically upregulated by cell shrinkage.
“SGK1 is genomically upregulated by cell shrinkage and by a variety of hormones including mineralocorticoids and glucocorticoids.”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
Increased cytosolic Ca2+ activity and NO are among the regulators that control SGK1 transcription.
“SGK1 transcription is controlled by a wide variety of additional hormones and further regulators including increase of cytosolic Ca 2+ activity and NO (Lang et al. 2006(Lang et al. , 2009)).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
Dehydration alters SGK1 expression.
“Dehydration alters the expression of a wide variety of genes (Mutsuga et al. 2005;Lee et al. 2006;Ramos et al. 2007;Hindmarch et al. 2008;Wang et al. 2009;Bourassa & Speth, 2010;Brocker et al. 2010;Pereira-Derderian et al. 2010;Scott & Brown, 2010) including SGK1 (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
Cerebral SGK1 expression is further upregulated by dehydration.
“Presumably due to cell volume sensitivity of SGK1 transcription, cerebral SGK1 expression is further upregulated by dehydration (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 increases the protein abundance and/or activity of a variety of ion channels, carriers, and the Na+/K+-ATPase.
“SGK1 increases the protein abundance and/or activity of a variety of ion channels (e.g.SCN5A, ENaC, ASIC1, TRPV5,6, ROMK, Kv1.1-5, KCNE1/KCNQ1, KCNQ2-5, GluR6, VSOAC, ClC2, CFTR), carriers (e.g.NHE3, NKCC2, NCC, NaPiIIb, SMIT, GLUT1,4, SGLT1, NaDC, EAAT1-5, SN1, ASCT2, 4F2/LAT, PepT2, CreaT), and the Na + /K + -ATPase”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 is activated by insulin and growth factors via PI3-kinase, PDK1, and mTORC2.
“The kinase is activated by insulin and growth factors via PI3-kinase, the 3-phosphoinositide-dependent kinase PDK1, and the mammalian target of rapamycin mTORC2 (Lang et al. 2006(Lang et al. , 2009;;Peterson et al. 2009).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
The dehydration-induced upregulation of cerebral SGK1 expression is presumably due to cell volume sensitivity of SGK1 transcription.
“Presumably due to cell volume sensitivity of SGK1 transcription, cerebral SGK1 expression is further upregulated by dehydration (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
Hippocampal SGK1 expression is stimulated by fear conditioning, elevated plus maze exposure, and enrichment training.
“Hippocampal SGK1 expression is stimulated by fear conditioning, elevated plus maze exposure and after enrichment training (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 transcript levels are enhanced by amphetamine, LSD, neuronal injury, neuronal excitotoxicity, and microgravity.
“SGK1 transcript levels are further enhanced by the psychostimulant amphetamine, by the hallucinogenic drug lysergic acid dimethylamide (LSD), by neuronal injury, neuronal excitotoxicity and microgravity (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
Transfection of inactive SGK1 impairs spatial learning, fear-conditioning learning, and novel object recognition learning in rats.
“In those animals transfection of inactive SGK1 impairs spatial learning, fear-conditioning learning, and novel object recognition learning (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 is involved in the pathophysiology of neurodegeneration.
“SGK1 is further involved in the pathophysiology of allergy, peptic ulcer, tumour growth, fibrosing disease, ischaemia and neurodegeneration (Lang et al. 2006(Lang et al. , 2009)).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
Transfection of wild-type SGK1 improves learning abilities of rats.
“Transfection of wild-type SGK1 improves, and transfection of inactive SGK1 decreases, the learning abilities of rats (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 contributes to the regulation of transport, hormone release, neuroexcitability, inflammation, cell proliferation and apoptosis.
“SGK1 contributes to the regulation of transport, hormone release, neuroexcitability, inflammation, cell proliferation and apoptosis (Lang et al. 2006(Lang et al. , 2009)).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 stimulation of dendrite growth may impact on learning abilities.
“SGK1 stimulates dendrite growth, which may impact on learning abilities (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
Hippocampal SGK1 mRNA abundance is increased in fast-learning compared to slow-learning rats.
“Moreover, hippocampal SGK1 mRNA abundance is increased in fast-learning when compared to slow-learning rats (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 stimulates dendrite growth.
“SGK1 stimulates dendrite growth, which may impact on learning abilities (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
Transfection of inactive SGK1 decreases learning abilities of rats.
“Transfection of wild-type SGK1 improves, and transfection of inactive SGK1 decreases, the learning abilities of rats (Lang et al. 2006).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
SGK1 regulates several enzymes and transcription factors.
“SGK1 regulates several enzymes (e.g.glycogensynthase-kinase-3, ubiquitin-ligase Nedd4-2, phosphomannose-mutase-2) and transcription factors (e.g.FKHRL1/Foxo3a, β-catenin, NFκB, p53) (Lang et al. 2006(Lang et al. , 2009)).”
From Significance of SGK1 in the regulation of neuronal function (2010) · cites this paper as Lang et al. 2006
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The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission
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NEDD4-2 (NEDD4L): The ubiquitin ligase for multiple membrane proteins
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The role of the BK channel in potassium homeostasis and flow-induced renal potassium excretion
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SGK1 inhibition induces autophagy-dependent apoptosis via the mTOR-Foxo3a pathway
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Self-citationSGK1 inhibition in glia ameliorates pathologies and symptoms in Parkinson disease animal models
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PDK1: The Major Transducer of PI 3-Kinase Actions
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Mori, S., Nada, S., Kimura, H., Tajima, S., Takahashi, Y., Kitamura, A., Oneyama, C., & Okada, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088891 · Cited by 106 · see citing works
Lang, F. J. W., Görlach, A., & Vallon, V. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903260807 · Cited by 106 · see citing works
Self-citationAmato, R., D’Antona, L., Porciatti, G., Agosti, V., Menniti, M., Rinaldo, C., Costa, N., Bellacchio, E., Mattarocci, S., Fuiano, G., et al. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0525-5 · Cited by 103 · see citing works
Self-citationThe acute muscle swelling effects of blood flow restriction
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Schmidt, S., Liu, G., Liu, G., Yang, W., Honisch, S., Pantelakos, S., Stournaras, C., Hönig, A., & Lang, F. J. W. (2014) · Oncotarget · doi:10.18632/oncotarget.2035 · Cited by 96 · see citing works
Self-citationRictor Forms a Complex with Cullin-1 to Promote SGK1 Ubiquitination and Destruction
Gao, D., Wan, L., Inuzuka, H., Berg, A. H., Tseng, A., Zhai, B., Shaik, S., Bennett, E. J., Tron, A. E., Gasser, J. A., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.08.016 · Cited by 94 · see citing works
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SGK1 in Human Cancer: Emerging Roles and Mechanisms
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Blood flow restriction: An evidence based progressive model (Review)
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Frontier of Epilepsy Research - mTOR signaling pathway
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Up-regulation of FGF23 release by aldosterone
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Self-citationSerum and glucocorticoid inducible kinase, metabolic syndrome, inflammation, and tumor growth
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Self-citationTherapeutic potential of serum and glucocorticoid inducible kinase inhibition
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Self-citationThe mTOR Signaling Pathway in the Brain: Focus on Epilepsy and Epileptogenesis
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Genome Scan for Determinants of Serum Uric Acid Variability
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Regulation of Ion Channels by Membrane Lipids
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Stimulation of Ca 2+ ‐channel Orai1/STIM1 by serum‐and glucocorticoid‐inducible kinase 1 (SGK1)
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Self-citationColorectal carcinoma cells—Regulation of survival and growth by SGK1
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Self-citationBoehmer, C., Laufer, J., Jeyaraj, S., Klaus, F., Lindner, R., Lang, F., & Palmada, M. (2008) · Cellular Physiology and Biochemistry · doi:10.1159/000185543 · Cited by 82 · see citing works
Self-citationAldosterone-Stimulated SGK1 Activity Mediates Profibrotic Signaling in the Mesangium
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Identification of STAT5A and STAT5B Target Genes in Human T Cells
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Glycogen synthase kinase-3β: a promising candidate in the fight against fibrosis
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Non-genomic effect of glucocorticoids on cardiovascular system
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Aldosterone and glomerular podocyte injury
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mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity
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Self-citationMacrophages in homeostatic immune function
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Stookey, J. D., Kavouras, S. A., Suh, H., & Lang, F. J. W. (2020) · Nutrients · doi:10.3390/nu12040905 · Cited by 76 · see citing works
Self-citationMammalian TOR signaling to the AGC kinases
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- Authors
- Lang, F., Böhmer, C., Palmada, M., Seebohm, G., Strutz-Seebohm, N., & Vallon, V.
- Affiliations
- University of Tübingen (DE)
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2006-10
- Volume
- 86
- Issue
- 4
- Pages
- 1151-1178
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2111123535
- Cited by
- 689
- References
- 396
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 19 · 2023: 25 · 2022: 34 · 2021: 29 · 2020: 28 · 2019: 29 · 2018: 28 · 2017: 33 · 2016: 38 · 2015: 30 · 2014: 42 · 2013: 39 · 2012: 50
- FWCI
- 3.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 56248, DK70667, R01DK056248, R21DK070667)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- serum- and glucocorticoid-inducible kinase, SGK1, SGK2, SGK3, kinase isoforms, metabolic syndrome, ion transport regulation, Na+/K+-ATPase, Nedd4-2, forkhead transcription factor, β-catenin, NF-κB, salt sensitivity of blood pressure, salt appetite, glucose uptake, memory consolidation, cardiac repolarization, hair growth, tumor growth, neurodegeneration, fibrosis, ischemia
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Animals, Cardiovascular Diseases, Cardiovascular System, Humans, Isoenzymes, Kidney, Kidney Diseases, Protein Serine-Threonine Kinases, Immediate-Early Proteins
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