CoChat
Sign Up
Cited by 173Ion Transport and Channel RegulationIon channel regulation and functionNeuroscience and Neuropharmacology Research

Significance of SGK1 in the regulation of neuronal function

Open access
Lang, Florian, Strutz-Seebohm, Nathalie, Seebohm, Guiscard, Lang, Undine E.·2010·The Journal of Physiology
DOI 10.1113/jphysiol.2010.190926PMC PMC2988501
Open this paper in CoChat — free accountOpen PDF

Abstract

The present brief review highlights the putative role of the serum- and glucocorticoid-inducible-kinase-1 (SGK1) in the regulation of neuronal function. SGK1 is genomically upregulated by cell shrinkage and by a variety of hormones including mineralocorticoids and glucocorticoids. The kinase is activated by insulin and growth factors via phosphatidylinositide-3-kinase (PI3-kinase), phosphoinositide-dependent kinase PDK1 and mammalian target of rapamycin mTORC2. SGK1 upregulates ion channels (e.g. SCN5A, ENaC, ASIC1, TRPV5,6, ROMK, Kv1.1-5, KCNEx/KCNQ1-5, GluR6, VSOAC, ClC2, CFTR), carriers (e.g. NHE3, NKCC2, NCC, NaPiIIb, SMIT, GLUT1,4, SGLT1, NaDC, EAAT1-5, SN1, ASCT2, 4F2/LAT, PepT2), and the Na(+)/K(+)-ATPase. SGK1 regulates enzymes (e.g. glycogen-synthase-kinase-3, ubiquitin-ligase Nedd4-2, phosphomannose-mutase-2), and transcription factors (e.g. forkhead transcription factor Foxo3a, β-catenin, nuclear factor-kappa-B (NFB)). SGK1 participates in the regulation of transport, hormone release, neuroexcitability, inflammation, coagulation, cell proliferation and apoptosis. SGK1 contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Presumably, SGK1 contributes to the regulation of diverse cerebral functions (e.g. memory consolidation, fear retention) and the pathophysiology of several cerebral diseases (e.g. Parkinson's disease, schizophrenia, depression, Alzheimer's disease). Despite multiple SGK1 functions, the phenotype of the SGK1 knockout mouse is mild and becomes only apparent under challenging conditions.

AI snapshot

Written from the paper’s full text.

TL;DR

This brief review synthesizes evidence that serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates neuronal function through control of ion channels, carriers, enzymes and transcription factors, and may contribute to memory consolidation and several cerebral diseases. The authors conclude that compelling evidence implicates SGKs in brain disease pathophysiology, but whether SGK1 protects, promotes, or merely accompanies cell death remains unresolved.

Key findings

  • SGK1 is genomically upregulated by cell shrinkage (within ~20 min of osmotic and isotonic shrinkage) and by hormones including mineralocorticoids and glucocorticoids; it is activated by insulin and growth factors via PI3-kinase, PDK1 and mTORC2.
  • SGK1 upregulates numerous ion channels (e.g. SCN5A, ENaC, ASIC1, TRPV5/6, ROMK, Kv1.1-5, KCNQ1-5, GluR6, ClC2, CFTR), carriers (e.g. NHE3, NKCC2, NCC, GLUT1/4, SGLT1, EAAT1-5, CreaT) and the Na⁺/K⁺-ATPase, and regulates enzymes (glycogen-synthase-kinase-3, Nedd4-2, phosphomannose-mutase-2) and transcription factors (Foxo3a, β-catenin, NFκB, p53).
  • A common SGK1 gene variant (~3–5% prevalence in Caucasians, ~10% in Africans) is associated with increased blood pressure, obesity, enhanced diabetes prevalence and shortened cardiac action potential.
  • In neuronal contexts, transfection of wild-type SGK1 improves and inactive SGK1 decreases rat learning; inactive SGK1 impairs spatial, fear-conditioning and novel object recognition learning, and impairs fear retention, while constitutively active SGK1 enhances fear retention. SGK1 downregulates Hes5, stimulates dendrite growth, and upregulates AMPA and kainate receptors.
  • Despite multiple SGK1 functions, the SGK1 knockout mouse phenotype is mild and becomes apparent only under challenging conditions.

Methods

  • Narrative/brief review presented at The Journal of Physiology Symposium on Regulation of neuronal cell volume (Experimental Biology 2010, Anaheim, CA, USA, 26 April 2010); commissioned by the Editorial Board.
  • No primary data or systematic search strategy are reported; the authors state that "due to N limitations of references, reviews are quoted covering earlier papers," so much of the evidence is cited via prior reviews (e.g. Lang et al. 2006, 2009).
  • Synthesis covers SGK1 regulation and function, its putative neuronal roles (memory, fear retention, glutamate receptor/transporter effects, BDNF signalling, food intake) and its putative roles in neuronal disease (ALS, schizophrenia, epilepsy, Alzheimer's, Parkinson's, depression, Rett syndrome, ischaemia).

Limitations

  • Stated by the authors: it is "not certain, to what extent SGK1 protects from or stimulates cell death or is just an innocent bystander in those disorders," and "we are presently far from understanding the contribution of SGK1 to the deterioration or maintenance of neuronal function."
  • Stated by the authors: whether decreased SGK1 stimulation of glutamate carriers leads to pathophysiologically relevant decline of transporter function "remains to be shown."
  • Evident from the text: this is a non-systematic narrative review relying heavily on secondary citations and on speculative language ("presumably," "could," "at least in theory"), with no primary experiments, quantitative synthesis, or formal quality appraisal of the cited evidence.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1113/jphysiol.2010.190926

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

11 of 58 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured

  • Interpretationcitation

    The effects of osmotic states on seizure susceptibility are in part due to an osmotic gradient across the blood-brain barrier, leading to water movement and changes in extracellular space.

    “effects in part due to an osmotic gradient across the blood-brain barrier, leading to respective movements of water and changes of extracellular space (Cserr et al. 1991;Silver et al. 1996;Verkman, 2005).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Cserr et al. 1991 source

      The paper’s abstract (pp. 277–295; passage 3) reports osmotically induced water loss from rat cerebral cortex during acute hypernatremia. It concludes that extracellular space decreases as water and electrolytes are lost (passage 4). The available text does not establish an osmotic gradient specifically across the blood–brain barrier or link these changes to seizure susceptibility. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites Silver et al. 1996 source
    • cites Verkman, 2005 source
  • Premisecitation

    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”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Lang et al. 2006 source
    • cites Lang et al. , 2009 source
    • cites Boehmer et al. 2008a,b source
  • Premisecitation

    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).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Lang et al. 2006 source
    • cites Lang et al. , 2009 source
    • cites Peterson et al. 2009 source

      The Introduction (page not provided) says mTORC2 phosphorylates SGK1 in response to growth factors. It does not specify insulin or establish PI3K and PDK1 as steps in SGK1 activation. The Results passage on PI3K and PDK1 concerns Akt, not SGK1. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Premisecitation

    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)).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Lang et al. 2006 source
    • cites Lang et al. , 2009 source
  • Premisecitation

    Neuronal SGK1 expression is suppressed by Zif268 (Egr1/Krox24/NGF-IA).

    “Neuronal SGK1 expression is suppressed by Zif268 (Egr1/Krox24/NGF-IA), a transcription factor associated with neuronal plasticity (James et al. 2006).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites James et al. 2006 source
  • Classified as probably not a substantial claim. 5
  • May combine two claims. 9
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    SGK1 is ubiquitously expressed.

    “SGK1 is ubiquitously expressed (Lang et al. 2006(Lang et al. , 2009)).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Lang et al. 2006 source
    • cites Lang et al. , 2009 source

  • May combine two claims.

    Premisecitation

    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)).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Lang et al. 2006 source
    • cites Lang et al. , 2009 source

      The Introduction and “Regulation of SGK1 expression and activity” section say that many stimuli control SGK1 transcription. But the section describes increased cytosolic Ca2+ as activating SGK1, not controlling its transcription; the passages about NO describe SGK1 affecting nitric oxide production, not NO regulating SGK1 transcription. No page numbers are available in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    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)).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Lang et al. 2006 source
    • cites Lang et al. , 2009 source

  • May combine two claims.

    Premisecitation

    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)).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Lang et al. 2006 source
    • cites Lang et al. , 2009 source

      The Conclusions (page unavailable) say SGK1 participates in regulating epithelial transport, excitability, cell proliferation and apoptosis, and plays a role in inflammation. Our copy does not establish that SGK1 regulates hormone release; it also does not specify that the excitability mentioned is neuronal. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Stimulation of K+ channels and Cl- channels would counteract RVI and rather support regulatory cell volume decrease (RVD).

    “Stimulation of K + channels and Cl -channels, however, would counteract RVI and rather support regulatory cell volume decrease (RVD) (Lang et al. 1998;Hoffmann et al. 2009).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Lang et al. 1998 source
    • cites Hoffmann et al. 2009 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Hydration may modify cerebral function by influencing neuronal or glial cell volume.

    “Hydration may further modify cerebral function by influencing neuronal or glial cell volume (Lang et al. 1998).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lang et al. 1998 source

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    SGK1 presumably contributes to the pathophysiology of several cerebral diseases, including Parkinson's disease, schizophrenia, depression, and Alzheimer's disease.

    “consolidation, fear retention) and the pathophysiology of several cerebral diseases (e.g.Parkinson's disease, schizophrenia, depression, Alzheimer's disease).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: SGK1 contributes to memory consolidation.
    • Rests on an assumption: SGK1 participates in the regulation of neuroexcitability.
    • Rests on an assumption: SGK1 upregulates ion channels such as SCN5A, ENaC, ASIC1, TRPV5/6, ROMK, Kv1.1-5, KCNEx/KCNQ1-5, GluR6, VSOAC, ClC2, and CFTR.

  • May combine two claims. The quote only partly states this claim.

    Interpretationreasoning

    SGK1 presumably contributes to the regulation of diverse cerebral functions, including memory consolidation and fear retention.

    “Presumably, SGK1 contributes to the regulation of diverse cerebral functions (e.g.memory”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: SGK1 contributes to memory consolidation.
    • Rests on an assumption: SGK1 participates in the regulation of neuroexcitability.
    • Rests on an assumption: SGK1 upregulates ion channels such as SCN5A, ENaC, ASIC1, TRPV5/6, ROMK, Kv1.1-5, KCNEx/KCNQ1-5, GluR6, VSOAC, ClC2, and CFTR.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    SGK1-sensitive functions presumably contribute significantly to altered function of the dehydrated brain.

    “SGK1-sensitive functions presumably contribute significantly to altered function of the dehydrated brain.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lang et al. 2006 source

  • May combine two claims.

    Interpretationreasoning

    SGK1 presumably enhances the cellular capacity for both regulatory cell volume increase (RVI) and regulatory cell volume decrease (RVD).

    “SGK1 presumably enhances the cellular capacity for both RVI and RVD but is presumably not involved in the rapid activation of cell volume regulatory mechanisms, which is accomplished by activation of other kinases.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Cerebral SGK1 is upregulated by glucocorticoids, corticotropin releasing hormone, hyperactivity, intracranial self-stimulation, chronic escalating morphine regimen, and clozapine.

    “Cerebral SGK1 is upregulated by glucocorticoids (Sato et al. 2008;Sarabdjitsingh et al. 2010), corticotropin releasing hormone (Sheng et al. 2008), hyperactivity (Kalinichev et al. 2008), intracranial self-stimulation (Huguet et al. 2009), chronic escalating morphine regimen (Befort et al. 2008) and administration of the antipsychotic drug clozapine (Robbins et al. 2008).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Sato et al. 2008 source
    • cites Sarabdjitsingh et al. 2010 source
    • cites Sheng et al. 2008 source

  • May combine two claims.

    Premisecitation

    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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lang et al. 2006 source

  • May combine two claims.

    Premisecitation

    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).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lang et al. 2006 source
14 of 14

  • The paper relies on this without support.

    SGK1 contributes to memory consolidation.

    “SGK1 contributes to regulation of renal Na + retention, renal K + elimination, salt appetite, gastric acid secretion, intestinal Na + /H + exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation.”

  • The paper relies on this without support.

    SGK1 participates in the regulation of neuroexcitability.

    “SGK1 participates in the regulation of transport, hormone release, neuroexcitability, inflammation, coagulation, cell proliferation and apoptosis.”

  • The paper relies on this without support.

    SGK1 upregulates ion channels such as SCN5A, ENaC, ASIC1, TRPV5/6, ROMK, Kv1.1-5, KCNEx/KCNQ1-5, GluR6, VSOAC, ClC2, and CFTR.

    “SGK1 upregulates ion channels (e.g.SCN5A, ENaC, ASIC1, TRPV5,6, ROMK, Kv1.1-5, KCNEx/KCNQ1-5, GluR6, VSOAC, ClC2, CFTR)”

  • The paper relies on this without support.

    Multiple additional physiological and pathophysiological regulators of SGK1 expression and function exist.

    “Beyond that multiple additional physiological and pathophysiological regulators of SGK1 expression and function are known which may modify cerebral function in the absence of neuronal or glial cell volume changes.”

  • The paper relies on this without support.

    Rapid activation of cell volume regulatory mechanisms is accomplished by activation of other kinases.

    “SGK1 presumably enhances the cellular capacity for both RVI and RVD but is presumably not involved in the rapid activation of cell volume regulatory mechanisms, which is accomplished by activation of other kinases.”

  • The paper relies on this without support.

    Cell shrinkage upregulates SGK1.

    “Thus, upregulation of SGK1 by cell shrinkage may support RVI.”
6 of 6

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Opposite effects on long-term potentiation expression

    Minor

    The text says constitutively active SGK1 impairs the expression of long-term potentiation, but the title of the cited Ma et al. paper says SGK facilitates its expression. The descriptions give opposite directions for the cited effect.

1 of 1

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Lang, F., Strutz-Seebohm, N., Seebohm, G., & Lang, U. E.
Affiliations
  • University of Tübingen (DE)
  • Ruhr University Bochum (DE)
  • Stiftung Charité
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2010-09-15
Volume
588
Issue
18
Pages
3349-3354
ISSN
0022-3751 (ISSN-L)
DOI
10.1113/jphysiol.2010.190926
PMC
PMC2988501
OpenAlex
W2126405504
Semantic Scholar
796aabbb18044019a8f000242175f02846ae873b
Cited by
170
References
52
Citations by year
2026: 10 · 2025: 11 · 2024: 21 · 2023: 10 · 2022: 6 · 2021: 14 · 2020: 7 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 14 · 2015: 17 · 2014: 6 · 2013: 12 · 2012: 8
FWCI
3.07
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 1812 d)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
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
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
SGK1, serum- and glucocorticoid-inducible kinase, neuronal function, ion channels, ion transporters, Na+/K+-ATPase, PI3K signaling, mTORC2, PDK1, FOXO3, β-catenin, NF-κB, memory consolidation, neuronal excitability, neuroinflammation, apoptosis, salt sensitivity of blood pressure, Parkinson's disease, schizophrenia, depression, Alzheimer's disease
MeSH terms
Serum-Glucocorticoid Regulated Kinases, Animals, Neurons, Signal Transduction, Gene Expression Regulation, Enzymologic, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-18.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-18.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review