Affinage

SGK3

Serine/threonine-protein kinase Sgk3 · UniProt Q96BR1

Round 2 corrected
Length
496 aa
Mass
57.1 kDa
Annotated
2026-04-28
125 papers in source corpus 43 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SGK3 is a PI3K-dependent AGC family serine/threonine kinase that is uniquely recruited to endosomes via PtdIns(3)P binding to its N-terminal PX domain, where it undergoes allosteric activation and sequential phosphorylation by PDK1 (Thr-320) and mTORC2 (Ser-486) (PMID:10548550, PMID:16790420, PMID:34181950). PtdIns(3)P is supplied by Vps34-mediated synthesis at endosomes and by sequential dephosphorylation of PtdIns(3,4,5)P3 via SHIP1/2 and INPP4B, enabling SGK3 to function as a critical Akt-independent effector of oncogenic PI3K signaling that phosphorylates TSC2 to reactivate mTORC1, NDRG1 to promote its Fbw7-mediated degradation, Nedd4-2 to increase surface abundance of ion channels and transporters (ENaC, hERG, SGLT1), AIP4 to inhibit CXCR4 lysosomal sorting, and endosomal SNAREs (STX7, STX12) to regulate vesicle fusion (PMID:25177796, PMID:27481935, PMID:25458846, PMID:16888620, PMID:31665227). SGK3 cooperates with Akt2 in β-catenin–dependent hair follicle morphogenesis and pancreatic β-cell function, and its transcriptional upregulation by ERα and AR in hormone-dependent cancers drives resistance to PI3K, Akt, and aromatase inhibitors (PMID:15240817, PMID:21980074, PMID:21084382, PMID:31182914). A loss-of-function splice mutation eliminating the PDK1 phosphorylation site causes autosomal dominant hypophosphatemic rickets, establishing SGK3 as essential for renal phosphate homeostasis (PMID:31821448).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Identification of SGK3 as a novel PDK1-activated AGC kinase isoform established that the SGK family contains three members with distinct regulation—unlike SGK1, SGK3 is not serum- or glucocorticoid-inducible.

    Evidence Molecular cloning, in vitro kinase reconstitution with PDK1, site-directed mutagenesis, Northern blotting across human tissues

    PMID:10548550 PMID:10585774

    Open questions at the time
    • No endogenous substrate identified
    • No information on upstream lipid signals governing activation
    • Tissue-specific functions unknown
  2. 2001 High

    Discovery that the PX domain binds phosphoinositides and is required for endosomal targeting and kinase activity resolved the question of how SGK3 is spatially regulated and distinguished it from SGK1/SGK2.

    Evidence Lipid-binding assays, confocal live-cell imaging, PX domain mutagenesis ablating both localization and activity

    PMID:11514587

    Open questions at the time
    • Specific phosphoinositide species driving endosomal activation not determined
    • Structural basis of PX-phosphoinositide interaction unknown
    • Identity of the kinase phosphorylating the hydrophobic motif unresolved
  3. 2004 High

    Sgk3 knockout mice revealed an essential in vivo role in β-catenin–dependent hair follicle morphogenesis, providing the first genetic loss-of-function phenotype and linking SGK3 to Wnt/β-catenin signaling.

    Evidence Gene-targeted KO mice with histology, BrdU proliferation, β-catenin immunostaining, Lef-1 reporter in keratinocytes

    PMID:15240817 PMID:16103225

    Open questions at the time
    • Direct SGK3 substrate mediating β-catenin nuclear accumulation not identified
    • Whether SGK3 phosphorylates GSK-3β in vivo to stabilize β-catenin not confirmed
    • Redundancy with Akt isoforms not yet tested
  4. 2004 Medium

    Demonstration that SGK3 stimulates ENaC, SGLT1, and other channels/transporters via Nedd4-2 phosphorylation established a general mechanism by which SGK3 increases surface transporter abundance through E3 ligase inhibition.

    Evidence Xenopus oocyte electrophysiology with constitutively active/inactive SGK3 mutants, Nedd4-2 phosphosite mutagenesis

    PMID:12632189 PMID:15166308

    Open questions at the time
    • All transporter studies performed in Xenopus oocytes, not mammalian cells
    • Relative contribution of Nedd4-2 versus other trafficking mechanisms unclear
    • In vivo relevance for most channels not established
  5. 2006 High

    Mechanistic dissection showed that PX domain-mediated endosomal recruitment is a prerequisite for PDK1 phosphorylation of Thr-320, and that artificially diverting SGK3 to the plasma membrane disrupts activation—demonstrating that SGK3 activation is spatially restricted to endosomes.

    Evidence Subcellular fractionation, phospho-specific antibodies, domain-swap chimeras, in vitro PDK1 kinase assay

    PMID:16790420

    Open questions at the time
    • Identity of the hydrophobic motif kinase still unresolved at this point
    • Structure of the PX-kinase domain interface unknown
    • How PDK1 accesses endosomal SGK3 not determined
  6. 2006 High

    SGK3 was shown to inhibit CXCR4 lysosomal sorting by phosphorylating the E3 ligase AIP4 at endosomes, providing the first direct evidence that endosomal SGK3 regulates receptor trafficking and degradation.

    Evidence Co-IP, confocal colocalization, in vitro kinase assay identifying AIP4 phosphosites, siRNA knockdown, CXCR4 degradation assay

    PMID:16888620

    Open questions at the time
    • AIP4 phosphosites not mapped to specific residues in this study
    • Whether SGK3 regulates trafficking of other GPCRs unknown
    • In vivo significance of CXCR4 stabilization not tested
  7. 2009 High

    Akt2/SGK3 double-knockout mice demonstrated functional redundancy between the two kinases in hair follicle β-catenin signaling, establishing that AGC kinases cooperate to maintain Wnt pathway output in vivo.

    Evidence Double-KO mouse genetics with β-catenin immunostaining, BrdU labeling, Lef-1 reporter

    PMID:19433625

    Open questions at the time
    • Whether the redundancy extends to other tissues remains untested
    • Direct shared substrates mediating β-catenin stabilization not identified
  8. 2014 High

    Use of a selective Vps34 inhibitor (VPS34-IN1) proved that Vps34-generated PtdIns(3)P is the primary endosomal lipid activating SGK3, while a second PtdIns(3)P pool derived from class I PI3K product dephosphorylation (via SHIP1/2, INPP4B) also contributes, resolving the upstream lipid input question.

    Evidence VPS34-IN1 inducing rapid SGK3 dephosphorylation, class I PI3K inhibitors causing partial SGK3 loss, PX domain mutant epistasis

    PMID:25177796

    Open questions at the time
    • Relative flux through each PtdIns(3)P-generating pathway not quantified
    • Cell-type variation in pathway dependency unknown
  9. 2014 High

    SGK3 was identified as an amplified oncogene in breast cancer activated via INPP4B-dependent, Akt-independent PI3K signaling; it promotes tumorigenesis by phosphorylating NDRG1 for Fbw7-mediated degradation, establishing SGK3 as a driver of PI3K oncogenic signaling that can bypass Akt.

    Evidence Genomic copy-number analysis, siRNA, 3D Matrigel, xenograft, NDRG1 ubiquitination and degradation assays

    PMID:25458846

    Open questions at the time
    • Whether NDRG1 phosphorylation is sufficient for tumor-promoting effects not determined
    • Patient stratification biomarkers for SGK3-driven tumors not developed
  10. 2016 High

    The critical question of how cancer cells resist PI3K/Akt inhibitors was answered by showing that prolonged inhibition upregulates SGK3, which phosphorylates TSC2 to reactivate mTORC1 independently of Akt, providing the mechanistic basis for drug resistance.

    Evidence Prolonged PI3K/Akt inhibitor treatment, phospho-SGK3/TSC2/S6K Western blotting, siRNA epistasis, BT-474 xenograft with dual SGK+Akt inhibitor

    PMID:27481935

    Open questions at the time
    • Specific TSC2 phosphosite(s) targeted by SGK3 not fully mapped
    • Clinical validation of combined SGK3+Akt inhibition not yet performed
  11. 2019 High

    Phosphoproteomics identified endosomal SNAREs (STX7, STX12) as SGK3-specific substrates poorly phosphorylated by Akt, revealing that SGK3 directly regulates endosomal membrane fusion and explaining its unique endosomal function.

    Evidence Quantitative phosphoproteomics, in vitro kinase assays with substrate specificity comparison, SGK3 CRISPR KO, Co-IP of STX12/SNARE complex

    PMID:31665227

    Open questions at the time
    • Functional consequence of STX7 phosphorylation on trafficking not characterized
    • Whether SNARE phosphorylation contributes to SGK3 oncogenic functions unknown
  12. 2020 Medium

    A human SGK3 splice mutation eliminating the PDK1 phosphorylation site was shown to cause autosomal dominant hypophosphatemic rickets, establishing SGK3 as essential for renal phosphate handling and providing the first Mendelian disease link.

    Evidence Exome sequencing with family co-segregation, RT-PCR splice assay confirming exon 13 skipping and loss of Thr-320

    PMID:31821448

    Open questions at the time
    • No functional reconstitution (e.g., kinase activity of mutant protein, rescue in cells)
    • Mechanism linking SGK3 to phosphate reabsorption not yet identified at molecular level
    • Single family reported
  13. 2021 High

    In vitro reconstitution with HDX-MS revealed the allosteric mechanism of SGK3 activation: PtdIns(3)P binding to the PX domain induces large conformational changes that expose the activation loop, explaining why membrane recruitment and phosphorylation are obligatorily coupled.

    Evidence HDX-MS structural analysis, liposome reconstitution with Vps34, SPR/ITC biophysics

    PMID:34181950

    Open questions at the time
    • No high-resolution crystal or cryo-EM structure of full-length SGK3 available
    • Conformational dynamics during substrate engagement not resolved
  14. 2023 High

    SGK3 was shown to function as an antioxidant regulator by directly phosphorylating catalase to promote its tetrameric active state and by phosphorylating GSK-3β to prevent β-TrCP-mediated catalase degradation, linking SGK3 to redox homeostasis and chemoresistance.

    Evidence In vitro kinase assay, Co-IP, native PAGE for catalase tetramer, ubiquitination assay, ROS measurement, drug combination assays in PIK3CA-mutant cervical cancer cells

    PMID:37866161

    Open questions at the time
    • Catalase phosphosite(s) not mapped
    • In vivo relevance of SGK3-catalase axis not tested
    • Generalizability beyond PIK3CA-mutant cervical cancer unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the high-resolution structure of full-length SGK3, whether SGK3 endosomal SNARE phosphorylation contributes to its oncogenic functions, clinical validation of combined SGK3/Akt/PI3K inhibitor strategies, and the molecular mechanism by which SGK3 loss causes hypophosphatemic rickets.
  • No full-length SGK3 atomic structure
  • Clinical-grade selective SGK3 inhibitor not yet available
  • Mechanism of SGK3-dependent renal phosphate reabsorption uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0008289 lipid binding 3
Localization
GO:0005768 endosome 6 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 6 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-382551 Transport of small molecules 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
AIP4GSK3BNDRG1NEDD4LPDPK1STX12STX7TSC2

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 SGK3 (SGKL/CISK) was cloned and characterized as a novel isoform of SGK with a catalytic domain 80% identical to SGK1 and SGK2; it is activated in vitro by PDK1 via phosphorylation of Thr-253 (activation loop), and this activation is potentiated by mutation of Ser-419 to Asp (hydrophobic motif site). SGK3 mRNA is ubiquitously expressed and is not upregulated by serum or glucocorticoids. Molecular cloning, in vitro kinase assays, site-directed mutagenesis, Northern blotting The Biochemical journal High 10548550
1999 SGK3 (SGKL) was mapped to human chromosome 8q12.3-q13.1 and encodes a protein sharing 67% amino acid identity with rat SGK and 66% with human SGK1; a 4.4-kb transcript is detected in 16 human tissues with highest abundance in lung. Molecular cloning, radiation hybrid mapping, Northern blotting Genomics Medium 10585774
2001 The PX domain of CISK/SGK3 binds phosphoinositides including PtdIns(3,5)P2 and PtdIns(3,4,5)P3 and is required for targeting SGK3 to the endosomal compartment. Mutation of the PX domain that abolishes phospholipid binding disrupts endosomal localization and decreases SGK3 kinase activity in vivo, demonstrating that the PX domain regulates SGK3 localization and activity through phosphoinositide interaction. Lipid-binding assays, confocal live-cell imaging, PX domain mutagenesis, kinase activity assays The Journal of cell biology High 11514587
2002 SGK3 (SGKL) phosphorylates GSK-3β at Ser-9 in vitro and interacts with GSK-3β, as identified by yeast two-hybrid screening and confirmed by co-immunoprecipitation in HEK293 cells; wild-type but not kinase-dead SGK3 is required for this phosphorylation. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay with phospho-specific antibody Biochemical and biophysical research communications Medium 12054501
2003 SGK2 and SGK3 stimulate the epithelial Na+ channel ENaC in Xenopus oocytes, increasing amiloride-sensitive current comparably to SGK1. Mutation of the SGK consensus phosphorylation site in α-ENaC (S622A) did not abolish the stimulatory effect, indicating SGK3 acts through indirect mechanisms rather than direct phosphorylation of the channel subunit. Dual-electrode voltage-clamp in Xenopus oocytes, site-directed mutagenesis Pflugers Archiv : European journal of physiology Medium 12632189
2004 SGK3 stimulates the Na+-coupled glucose transporter SGLT1 in Xenopus oocytes and phosphorylates Nedd4-2; the constitutively active isoform SGK3 enhances SGLT1-mediated glucose-induced current and reverses the inhibitory effect of co-expressed Nedd4-2. Deletion of SGK/PKB phosphorylation sites in Nedd4-2 blunted kinase effects, placing Nedd4-2 as a direct SGK3 substrate in this pathway. Xenopus oocyte electrophysiology, in vitro kinase assay, Nedd4-2 mutagenesis Obesity research Medium 15166308
2004 Targeted disruption of Sgk3 in mice causes defective postnatal hair follicle morphogenesis. Null mice show reduced proliferation and loss of nuclear β-catenin accumulation in hair bulb keratinocytes; heterologous expression of SGK3 in cultured keratinocytes potently modulates β-catenin/Lef-1-mediated gene transcription, establishing a role for SGK3 in the β-catenin pathway during hair follicle development. Gene-targeted knockout mice, histology, BrdU proliferation assay, immunostaining for β-catenin, luciferase reporter assay in keratinocytes Molecular biology of the cell High 15240817
2004 SGK3 regulates the epithelial Ca2+ channel TRPV5 in Xenopus oocytes: co-expression of SGK3 with TRPV5 and NHERF2 stimulates Ca2+ uptake and Ca2+-induced currents. The effect is mimicked by SGK1 but not by SGK2 or PKB, and requires kinase activity (inactive SGK1 K127N is ineffective). Xenopus oocyte electrophysiology, tracer Ca2+ flux, kinase-dead mutants Cellular physiology and biochemistry Medium 15319523
2005 Sgk3 knockout mice display decreased intestinal Na+-coupled glucose transport as measured in Ussing chamber preparations, lower fasting plasma glucose, and increased food intake, establishing SGK3 as required for adequate intestinal SGLT1-mediated glucose absorption in vivo. Sgk3 knockout mice, Ussing chamber electrophysiology, plasma glucose measurements Pflugers Archiv : European journal of physiology High 15971077
2005 SGK3 links growth factor signaling to maintenance of transiently amplifying hair follicle matrix progenitor cells; Sgk3-null mice show reduced proliferation, increased apoptosis, and premature follicle regression resembling a gain-of-function of EGF signaling. In cultured primary keratinocytes, Sgk3 negatively regulates PI3K signaling. Sgk3 knockout mice, BrdU/TUNEL labeling, growth factor stimulation in primary keratinocytes The Journal of cell biology High 16103225
2005 SGK1 and SGK3, but not SGK2 or PKB, increase SLC6A8 (creatine transporter) activity in Xenopus oocytes by increasing maximal transport rate without altering substrate affinity; constitutively active SGK3 (S419D) but not inactive (K119N) is effective. Xenopus oocyte electrophysiology, kinetic analysis, constitutively active/inactive mutants Biochemical and biophysical research communications Medium 16036218
2005 SGK3 increases EAAT5 (excitatory amino acid transporter 5) activity and cell-surface abundance in Xenopus oocytes by ~1.5–2-fold; PKB does not share this activity, indicating isoform specificity. Xenopus oocyte electrophysiology, chemiluminescence cell-surface assay Biochemical and biophysical research communications Medium 15737648
2006 Both a functional PX domain and PI3K activation are necessary for phosphorylation of SGK3 at Thr-320 (PDK1 site) and Ser-486 (hydrophobic motif). PDK1 phosphorylates endosome-associated SGK3 at Thr-320; diverting SGK3 to the plasma membrane interferes with PDK1 phosphorylation. A chimeric protein with the hydrophobic motif of PRK2 is constitutively active, and SGK3 activation becomes PX domain-independent once the HM is phosphorylated. Subcellular fractionation, phospho-specific antibodies, domain-swap chimeras, constitutively active/inactive mutants, in vitro PDK1 kinase assay The Journal of biological chemistry High 16790420
2006 SGK3 increases HERG (Kv11.1) channel current and plasma membrane protein abundance in Xenopus oocytes without affecting gating kinetics; SGK1 does not share this activity. Mutation of both SGK consensus sites in HERG decreases basal current but does not abolish the SGK3 stimulatory effect, suggesting an indirect mechanism involving increased channel abundance. Xenopus oocyte voltage-clamp, chemiluminescence surface expression, site-directed mutagenesis Cellular physiology and biochemistry Medium 17167223
2006 CISK/SGK3, activated downstream of PI3K-PDK1 on endosomes, attenuates lysosomal degradation of CXCR4 by inhibiting its sorting from early endosomes to lysosomes. CISK interacts and co-localizes with the E3 ubiquitin ligase AIP4, phosphorylates specific AIP4 sites in vitro, and this interaction and CISK kinase activity are both required for inhibition of CXCR4 degradation. Co-immunoprecipitation, confocal microscopy, in vitro kinase assay, siRNA knockdown, receptor degradation assays The EMBO journal High 16888620
2006 SGK3 and stargazin independently regulate GluR1 AMPA receptor surface expression and glutamate-induced currents in Xenopus oocytes via distinct pathways; their effects are additive (15.5-fold combined vs. ~4-fold each alone). Mutation of the SGK consensus site in stargazin does not prevent SGK3 from further stimulating GluR1 current. Xenopus oocyte voltage-clamp, Western blotting, site-directed mutagenesis Pflugers Archiv : European journal of physiology Medium 16485113
2006 Renal function in SGK1/SGK3 double-knockout mice reveals partial compensation between isoforms: double-null mice have lower blood pressure, higher aldosterone, and greater NaCl excretion during salt deprivation than either single knockout, demonstrating SGK1 and SGK3 cooperate in renal NaCl retention. Double-knockout mouse genetics, metabolic caging, blood pressure telemetry, plasma aldosterone measurement American journal of physiology. Regulatory, integrative and comparative physiology High 16537821
2009 Akt2 and SGK3 act redundantly in postnatal hair follicle development. Akt2/SGK3 double-knockout mice have markedly worse hair growth defects than either single knockout, with failure of matrix cell β-catenin nuclear accumulation and proliferation at morphogenesis onset. In keratinocytes, both Akt2 and SGK3 stimulate a β-catenin-LEF1 transcriptional reporter, indicating redundant regulation of this pathway. Double-knockout mouse genetics, immunostaining for β-catenin, BrdU proliferation, luciferase reporter assay FASEB journal High 19433625
2010 SGK3 is an estrogen receptor (ER) transcriptional target in breast cancer cells. ERα binds to two regions at the sgk3 locus (identified by ChIP-seq) and stimulates sgk3 promoter activity upon E2 stimulation. SGK3 knockdown reduces estrogen-mediated survival of MCF-7 cells, and SGK3 overexpression partially protects against antiestrogen-induced apoptosis. ChIP-seq, promoter-luciferase assays, siRNA knockdown, flow cytometry for apoptosis Molecular endocrinology High 21084382
2011 SGK3 and Akt2 double-knockout mice reveal a novel role of SGK3 in pancreatic β-cell function: DKO mice have worse glucose homeostasis than Akt2 single nulls due to impaired β-cell function (lower insulin/C-peptide, reduced β-cell mass, impaired glucose-stimulated insulin secretion), not increased insulin resistance. SGK3 is strongly expressed in normal islets and its loss dramatically reduces β-catenin expression in islets. Double-knockout mouse genetics, glucose/insulin tolerance tests, ELISA for insulin/C-peptide, β-cell mass morphometry Molecular endocrinology High 21980074
2012 SGK3 deficiency in dendritic cells reduces store-operated Ca2+ (SOC) entry triggered by thapsigargin, LPS, and CXCL12, decreases SOC channel currents, and lowers STIM2 protein abundance (without affecting Orai1, Orai2, STIM1, TRPC1). DC migration toward CXCL12 and CCL21 is impaired in sgk3−/− mice, linking SGK3 to STIM2-dependent SOC entry and chemotaxis. Sgk3 knockout bone-marrow-derived DCs, Ca2+ imaging (Fura-2), patch-clamp electrophysiology, Western blotting, migration transwell assays Cellular physiology and biochemistry High 23171960
2013 SGK1 and SGK3 increase hERG channel expression and current in HEK293 cells by phosphorylating and inhibiting Nedd4-2 AND by promoting Rab11-mediated hERG recycling. Disruption of the Nedd4-2 binding site in hERG only partially eliminates SGK effects; additional disruption of Rab11 completely eliminates the SGK-mediated increase, establishing a dual mechanism. hERG-HEK stable cell line, patch-clamp, Western blotting, ubiquitination assay, dominant-negative Rab11 The Journal of biological chemistry High 23589291
2014 SGK3 is the only protein kinase known to interact specifically with PtdIns(3)P via its PX domain. Mutations disrupting PtdIns(3)P binding ablate SGK3 kinase activity by preventing phosphorylation at both the T-loop (PDK1 site) and hydrophobic motif (mTOR site). The selective Vps34 inhibitor VPS34-IN1 induces rapid (~1 min) ~50–60% loss of SGK3 phosphorylation without affecting Akt, demonstrating that Vps34-generated PtdIns(3)P at endosomes is required for SGK3 activation. Class I PI3K inhibitors suppress SGK3 activity ~40%, suggesting a second PtdIns(3)P pool derived from dephosphorylation of PtdIns(3,4,5)P3 via SHIP1/2 and INPP4B. Selective Vps34 inhibitor (VPS34-IN1), PX domain point mutants, class I PI3K inhibitors (GDC-0941, BKM120), phospho-SGK3 immunoblotting in cells The Biochemical journal High 25177796
2014 SGK3 is amplified in breast cancer and activated downstream of PIK3CA in an INPP4B-dependent, Akt-independent manner. INPP4B expression leads to enhanced SGK3 activation with suppression of Akt phosphorylation. SGK3 is required for 3D proliferation, invasive migration, and tumorigenesis in vivo, and targets the metastasis suppressor NDRG1 for Fbw7-mediated degradation. Genomic copy-number analysis, PI3K inhibitors, siRNA knockdown, 3D Matrigel, xenograft tumor models, NDRG1 ubiquitination assays Molecular cell High 25458846
2014 SGK3 is an androgen receptor (AR) transcriptional target in prostate cancer cells. DHT/AR induces SGK3 expression requiring co-activation by estrogen receptor (ER); ER depletion blocks DHT-induced SGK3 expression. SGK3 knockdown decreases LNCaP proliferation by blocking G1-S transition, and SGK3 promotes p70 S6 kinase activation and increases cyclin D1 levels. ChIP, promoter-luciferase reporter, siRNA, flow cytometry cell-cycle analysis, Western blotting Molecular endocrinology High 24739041
2014 SGK3 upregulates the inwardly rectifying K+ channel Kir2.1 (KCNJ2) in Xenopus oocytes: wild-type and constitutively active S419D-SGK3 enhance Kir2.1-mediated currents and increase channel membrane protein abundance. The effect is abolished by SGK inhibitor EMD638683 and is independent of Na+/K+-ATPase. Brefeldin A experiments suggest SGK3 promotes channel insertion rather than preventing retrieval. Xenopus oocyte voltage-clamp, confocal immunostaining, chemiluminescence surface expression, brefeldin A insertion block Cellular physiology and biochemistry Medium 24556932
2015 PDK1 contributes to melanoma growth partly through SGK3; genetic or pharmacologic inhibition of PDK1 and SGK3 attenuates melanoma growth by inducing G1-phase cell-cycle arrest. Pan-PI3K inhibition synergizes with PDK1 inhibition, establishing SGK3 as an important mediator of PDK1 oncogenic activity in PTEN-wild-type melanoma. Genetic knockdown, pharmacologic inhibitors, cell-cycle analysis (FACS), xenograft models Cancer research Medium 25712345
2016 Prolonged PI3K or Akt inhibition in breast cancer cells leads to increased expression and activation of SGK3, which is controlled by hVps34-generated PtdIns(3)P binding to the PX domain. Under these conditions, SGK3 substitutes for Akt by phosphorylating TSC2 to activate mTORC1, thereby restoring mTORC1 signaling and proliferative output. A dual SGK+Akt inhibitor combination induced marked tumor regression in BT-474 xenografts. Prolonged drug treatment, Western blotting for phospho-SGK3 and mTORC1 substrates, TSC2 phosphorylation assays, siRNA, xenograft mouse model The EMBO journal High 27481935
2017 SGK3 promotes epithelial-mesenchymal transition in HCC cells and reduces phosphorylation-dependent degradation of β-catenin. miR-155 stimulates SGK3 expression by targeting and repressing P85α (a PI3K regulatory subunit), thereby removing its inhibitory effect on PI3K-AKT signaling, establishing a miR-155/PI3K/SGK3/β-catenin axis. miR-155 overexpression/inhibition, siRNA, Western blotting for EMT markers and β-catenin, luciferase reporter, immunofluorescence Oncotarget Medium 27602769
2017 SGK3 sustains ERα signaling in aromatase inhibitor (AI)-resistant breast cancer by maintaining SERCA2b function and endoplasmic reticulum (ER) homeostasis. The PERK arm of the ER stress response downregulates ERα expression; SGK3 prevents excessive ER stress, thereby retaining ERα expression and signaling and driving AI resistance. AI-resistant cell lines, siRNA knockdown, ER stress markers (PERK, ATF4), SERCA2b functional assays, ERα expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 28174265
2018 Endogenous SGK3 is rapidly activated by IGF1 through pathways involving both Class 1 and Class 3 PI3Ks: IGF1 enhances endosomal PtdIns(3)P via the UV-RAG/hVPS34 complex; Class 1 PI3K stimulates SGK3 through enhanced PtdIns(3)P production from dephosphorylation of PtdIns(3,4,5)P3 and through mTORC2-mediated phosphorylation of SGK3. Oncogenic Ras activates SGK3 solely through the Class 1 PI3K pathway. Endogenous SGK3 activation assays, selective Vps34 inhibitors, mTORC2 inhibitors/siRNA, PI3K inhibitors, phospho-SGK3 immunoblotting, PtdIns(3)P probes The Biochemical journal High 29150437
2019 SGK3 mediates rapamycin resistance in breast cancer by reactivating the mTORC1/4EBP1 axis: rapamycin activates SGK3 in a hVps34- and mTORC2-dependent manner, and SGK3 phosphorylates TSC2 to reactivate mTORC1, restoring 4EBP1 phosphorylation and cap-dependent translation. SGK3 deletion combined with Akt inhibition almost completely blocks 4EBP1 re-phosphorylation and suppresses growth in vivo. SGK3 CRISPR knockout, phosphoproteomics, xenograft, TSC2 phosphorylation assay, cap-dependent translation assay International journal of biological sciences High 31182914
2019 SGK3-PROTAC1, a PROTAC conjugate of an SGK inhibitor with a VHL ligand, selectively degrades SGK3 (not SGK1 or SGK2) within 2–8 h at 0.3 μM. Proteomic analysis shows SGK3 is the only cellular protein significantly reduced. SGK3 degradation suppresses phosphorylation of the SGK3 substrate NDRG1 and restores sensitivity of SGK3-dependent breast cancer cells to Akt and PI3K inhibitors, more effectively than conventional inhibition alone. PROTAC synthesis, quantitative proteomics, phospho-NDRG1 Western blotting, cell proliferation assays ACS chemical biology High 31461270
2019 Phosphoproteomic screens identified 40 novel SGK3 substrates including four endosomal proteins: STX7 (Ser126), STX12 (Ser139), RFIP4 (Ser527), and WDR44 (Ser346), which are efficiently phosphorylated in vitro by SGK3 but poorly by Akt due to an unfavorable n+1 residue. SGK3 phosphorylation of STX12 enhances its interaction with the VAMP4/VTI1A/STX6 SNARE complex and promotes STX12 plasma membrane localization. Quantitative phosphoproteomics, in vitro kinase assays, Phos-tag gel analysis, SGK3 CRISPR knockout, Co-immunoprecipitation, subcellular fractionation The Biochemical journal High 31665227
2020 PDPK1 (PDK1) mediates prostate cancer cell survival predominantly via SGK3 rather than Akt or SGK1: PDK1 knockdown significantly reduces SGK3 phosphorylation, and constitutively active SGK3 completely abrogates PDK1-knockdown-induced apoptosis, while constitutively active Akt does not, placing SGK3 as the primary survival effector of PDK1 in these cells. shRNA kinome library screen, siRNA, constitutively active SGK3/Akt rescue assays, PDK1 inhibitors, cell viability assays Journal of cellular and molecular medicine High 32926495
2020 A mutation in SGK3 (c.979-96 T>A) causes exon 13 skipping and in-frame deletion of 29 amino acids including Thr-320 (the PDK1 phosphorylation site required for activation), leading to autosomal dominant hypophosphatemic rickets. Protein structural modeling predicts significant structural change in the kinase domain, establishing SGK3 as a regulator of renal phosphate transport. Exome sequencing, co-segregation analysis, RT-PCR splice assay, protein structure modeling The Journal of clinical endocrinology and metabolism Medium 31821448
2021 In vitro reconstitution of SGK3 activation demonstrates that PtdIns(3)P binding to the PX domain induces large conformational changes in SGK3 that promote kinase activation, as revealed by hydrogen-deuterium exchange mass spectrometry. The PI3P-binding pocket of the PX domain is sequestered in the inactive conformation. SGK3 is regulated by a combination of phosphorylation and allosteric activation, and Vps34-mediated PtdIns(3)P synthesis on liposomes reconstitutes SGK3 activation in vitro. HDX-MS, in vitro reconstitution with liposomes + Vps34, biochemical activity assays, biophysics (SPR, ITC) The Journal of biological chemistry High 34181950
2021 SGK3 promotes vascular calcification in CKD by enhancing expression and activity of the sodium-dependent phosphate cotransporter Pit-1: SGK3 activates Pit-1 mRNA transcription via NF-κB, inhibits Nedd4-2-mediated Pit-1 ubiquitination/degradation, and directly phosphorylates Pit-1 at Thr468 (confirmed by co-immunoprecipitation and in vitro kinase assay) to enhance phosphate uptake independently of increased Pit-1 protein. Sgk3 knockdown in VSMCs, uremic mouse model (AVF/aorta), Co-IP, in vitro kinase assay, ubiquitination assay, NF-κB reporter Theranostics High 38169564
2022 CDK9 directly binds and activates SGK3, as identified by quantitative phosphoproteomics and pulldown assay, confirmed by co-immunoprecipitation. CDK9 promotes cardiac repair after myocardial infarction by directly activating SGK3 and the downstream GSK-3β/β-catenin pathway to stimulate cardiomyocyte cell cycle re-entry. Quantitative phosphoproteomics, pulldown assay, Co-IP, CDK9 overexpression/knockdown in cardiomyocytes, neonatal mouse apical resection/MI models Frontiers in cardiovascular medicine Medium 36082129
2023 SGK3 functions as an antioxidant factor in cervical cancer cells harboring PIK3CA helical domain mutations: SGK3 is activated by oxidative stress, interacts with and phosphorylates catalase to promote its tetrameric state and enzymatic activity, and phosphorylates GSK3β to protect catalase from GSK3β/β-TrCP-mediated ubiquitination and proteasomal degradation. SGK3 inhibition potentiates CDK4/6 inhibitor cytotoxicity and overcomes cisplatin resistance through ROS-mediated mechanisms. Co-IP, in vitro kinase assay, ubiquitination assay, native PAGE (tetramer analysis), ROS measurement, drug combination assays Redox biology High 37866161
2024 SGK3 deficiency in macrophages attenuates angiotensin II-induced cardiac remodeling. Mechanistically, SGK3 absence reduces IL-1β secretion by inhibiting the NLRP3/Caspase-1/IL-1β pathway in macrophages, which consequently suppresses Ndufa13 expression and mitochondrial oxidative stress in cardiomyocytes and fibroblasts. Macrophage-specific SGK3 conditional knockout (Lyz2-CRE) was used to establish macrophage-autonomous effects. Macrophage-specific SGK3 conditional KO (Lyz2-CRE), Ang II infusion cardiac model, RNA sequencing, NLRP3 inflammasome assays, co-culture system Cellular and molecular life sciences Medium 39158709
2025 SGK3 promotes β-catenin accumulation and ER+ breast cancer proliferation through a STAT3/ZMIZ2 axis: SGK3 activates STAT3, leading to ZMIZ2 transcription; ZMIZ2 binds and stabilizes β-catenin; SGK3 knockdown causes β-catenin polyubiquitination/degradation that is reversed by ZMIZ2 overexpression. Identified by proteomics as an SGK3 downstream target. Quantitative proteomics, ChIP (p-STAT3 at ZMIZ2 promoter), Co-IP (ZMIZ2-β-catenin), siRNA/overexpression, tissue microarray immunofluorescence British journal of pharmacology Medium 39876548
2025 SGK3 promotes breast cancer stemness and alpelisib resistance by activating the GSK3β/β-catenin signaling pathway; SGK3 is upregulated in alpelisib-resistant cells, and its inhibition restores sensitivity to alpelisib. Alpelisib-resistant cell model, Western blotting for GSK3β/β-catenin pathway, spheroid/tumor formation assays, SGK3 inhibitor treatment International journal of biological sciences Low 40303291
2024 SGK3 is required for TLR7 signaling in plasmacytoid dendritic cells: VPS34-IN1-mediated blockade of SGK3 endosomal recruitment prevents TLR7-dependent type-I IFN induction, identifying endosomal SGK3 as necessary for innate immune TLR7 signal transduction. VPS34-IN1 pharmacological inhibition, SGK3 localization assays, TLR7 stimulation, type-I IFN ELISA/reporter in human pDCs bioRxiv (preprint)preprint Low

Source papers

Stage 0 corpus · 125 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2000 Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proceedings of the National Academy of Sciences of the United States of America 707 11035810
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2001 Glycogen synthase kinase-3: properties, functions, and regulation. Chemical reviews 341 11749387
1999 Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. The Biochemical journal 335 10548550
2014 Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase. The Biochemical journal 254 25177796
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2001 Regulation and physiological roles of serum- and glucocorticoid-induced protein kinase isoforms. Science's STKE : signal transduction knowledge environment 188 11707620
2002 Convergence of multiple signaling cascades at glycogen synthase kinase 3: Edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase C-dependent intracellular pathway. Molecular and cellular biology 154 11884598
2001 Glucocorticoid activation of Na(+)/H(+) exchanger isoform 3 revisited. The roles of SGK1 and NHERF2. The Journal of biological chemistry 153 11751930
2004 Regulation of glucose transporter SGLT1 by ubiquitin ligase Nedd4-2 and kinases SGK1, SGK3, and PKB. Obesity research 150 15166308
2010 Second AKT: the rise of SGK in cancer signalling. Growth factors (Chur, Switzerland) 136 20919962
2011 Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. The Journal of biological chemistry 131 21832049
2014 SGK3 mediates INPP4B-dependent PI3K signaling in breast cancer. Molecular cell 128 25458846
2006 Sgk kinases and their role in epithelial transport. Annual review of physiology 125 16460280
2021 Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers. Nature genetics 116 34857952
2016 Pooled-matrix protein interaction screens using Barcode Fusion Genetics. Molecular systems biology 89 27107012
2001 Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides. The Journal of cell biology 89 11514587
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 88 32707033
2002 Ubiquitin modification of serum and glucocorticoid-induced protein kinase-1 (SGK-1). The Journal of biological chemistry 88 12218062
2002 Regulation of KCNE1-dependent K(+) current by the serum and glucocorticoid-inducible kinase (SGK) isoforms. Pflugers Archiv : European journal of physiology 81 12634932
2013 AKT-independent PI3-K signaling in cancer - emerging role for SGK3. Cancer management and research 78 24009430
2019 Design and Characterization of SGK3-PROTAC1, an Isoform Specific SGK3 Kinase PROTAC Degrader. ACS chemical biology 73 31461270
2003 The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel alpha,beta,gamma-ENaC. Pflugers Archiv : European journal of physiology 69 12632189
2004 Regulation of the epithelial Ca2+ channel TRPV5 by the NHE regulating factor NHERF2 and the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3 expressed in Xenopus oocytes. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 67 15319523
2016 The hVps34-SGK3 pathway alleviates sustained PI3K/Akt inhibition by stimulating mTORC1 and tumour growth. The EMBO journal 66 27481935
2010 SGK3 is an estrogen-inducible kinase promoting estrogen-mediated survival of breast cancer cells. Molecular endocrinology (Baltimore, Md.) 63 21084382
2002 K+ channel activation by all three isoforms of serum- and glucocorticoid-dependent protein kinase SGK. Pflugers Archiv : European journal of physiology 61 12397388
2004 Targeted disruption of the protein kinase SGK3/CISK impairs postnatal hair follicle development. Molecular biology of the cell 60 15240817
2015 Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis. Scientific reports 57 26392083
2006 CISK attenuates degradation of the chemokine receptor CXCR4 via the ubiquitin ligase AIP4. The EMBO journal 57 16888620
2023 SGK2 promotes prostate cancer metastasis by inhibiting ferroptosis via upregulating GPX4. Cell death & disease 56 36720852
2012 SGK3 regulates Ca(2+) entry and migration of dendritic cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 55 23171960
2004 Regulation of CLC-Ka/barttin by the ubiquitin ligase Nedd4-2 and the serum- and glucocorticoid-dependent kinases. Kidney international 54 15496163
2018 LncRNA SNHG5 promotes the progression of osteosarcoma by sponging the miR-212-3p/SGK3 axis. Cancer cell international 53 30250399
2010 The serum and glucocorticoid inducible kinases SGK1-3 stimulate the neutral amino acid transporter SLC6A19. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 52 20511718
2002 Activation of Na+/K+-ATPase by the serum and glucocorticoid-dependent kinase isoforms. Kidney & blood pressure research 51 12590200
2015 PDK1 and SGK3 Contribute to the Growth of BRAF-Mutant Melanomas and Are Potential Therapeutic Targets. Cancer research 49 25712345
2013 The serum- and glucocorticoid-inducible kinases SGK1 and SGK3 regulate hERG channel expression via ubiquitin ligase Nedd4-2 and GTPase Rab11. The Journal of biological chemistry 49 23589291
2006 Role of the Phox homology domain and phosphorylation in activation of serum and glucocorticoid-regulated kinase-3. The Journal of biological chemistry 49 16790420
2010 Kinase requirements in human cells: V. Synthetic lethal interactions between p53 and the protein kinases SGK2 and PAK3. Proceedings of the National Academy of Sciences of the United States of America 48 20616055
2005 Stimulation of the creatine transporter SLC6A8 by the protein kinases SGK1 and SGK3. Biochemical and biophysical research communications 46 16036218
2005 Sgk3 links growth factor signaling to maintenance of progenitor cells in the hair follicle. The Journal of cell biology 46 16103225
2018 MiRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS. Reproduction (Cambridge, England) 45 30328340
2017 MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma. Oncology reports 41 28849156
2015 INPP4B is upregulated and functions as an oncogenic driver through SGK3 in a subset of melanomas. Oncotarget 41 26573229
2015 MiR-212-3p inhibits glioblastoma cell proliferation by targeting SGK3. Journal of neuro-oncology 40 25720694
2019 Chemogenetic Activation of Prefrontal Cortex in Shank3-Deficient Mice Ameliorates Social Deficits, NMDAR Hypofunction, and Sgk2 Downregulation. iScience 39 31247448
2012 Serum and glucocorticoid kinase 3 at 8q13.1 promotes cell proliferation and survival in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 38 22262416
2006 Renal function of gene-targeted mice lacking both SGK1 and SGK3. American journal of physiology. Regulatory, integrative and comparative physiology 35 16537821
2006 Upregulation of HERG channels by the serum and glucocorticoid inducible kinase isoform SGK3. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 17167223
2021 Free CA125 promotes ovarian cancer cell migration and tumor metastasis by binding Mesothelin to reduce DKK1 expression and activate the SGK3/FOXO3 pathway. International journal of biological sciences 34 33613114
2016 MiR-155 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells through the activation of PI3K/SGK3/β-catenin signaling pathways. Oncotarget 32 27602769
2014 SGK3 is an androgen-inducible kinase promoting prostate cancer cell proliferation through activation of p70 S6 kinase and up-regulation of cyclin D1. Molecular endocrinology (Baltimore, Md.) 32 24739041
2007 Regulation of the epithelial calcium channel TRPV6 by the serum and glucocorticoid-inducible kinase isoforms SGK1 and SGK3. FEBS letters 31 18005662
2005 Regulation of the excitatory amino acid transporter EAAT5 by the serum and glucocorticoid dependent kinases SGK1 and SGK3. Biochemical and biophysical research communications 31 15737648
2018 Mechanism of activation of SGK3 by growth factors via the Class 1 and Class 3 PI3Ks. The Biochemical journal 30 29150437
2017 SGK3 sustains ERα signaling and drives acquired aromatase inhibitor resistance through maintaining endoplasmic reticulum homeostasis. Proceedings of the National Academy of Sciences of the United States of America 30 28174265
2002 Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct interaction. Biochemical and biophysical research communications 28 12054501
2019 Feedback Activation of SGK3 and AKT Contributes to Rapamycin Resistance by Reactivating mTORC1/4EBP1 Axis via TSC2 in Breast Cancer. International journal of biological sciences 27 31182914
2015 MiR-155 modulates the progression of neuropathic pain through targeting SGK3. International journal of clinical and experimental pathology 27 26823753
2021 Circ_0043532 regulates miR-182/SGK3 axis to promote granulosa cell progression in polycystic ovary syndrome. Reproductive biology and endocrinology : RB&E 25 34740363
2020 Phosphoinositide-dependent Kinase-1 (PDPK1) regulates serum/glucocorticoid-regulated Kinase 3 (SGK3) for prostate cancer cell survival. Journal of cellular and molecular medicine 24 32926495
2005 Decreased intestinal glucose transport in the sgk3-knockout mouse. Pflugers Archiv : European journal of physiology 24 15971077
2020 MiR-377-3p inhibits cell metastasis and epithelial-mesenchymal transition in cervical carcinoma through targeting SGK3. European review for medical and pharmacological sciences 23 32432732
2010 Heart 6-phosphofructo-2-kinase activation by insulin requires PKB (protein kinase B), but not SGK3 (serum- and glucocorticoid-induced protein kinase 3). The Biochemical journal 23 20687898
2012 SGK3 is associated with estrogen receptor expression in breast cancer. Breast cancer research and treatment 22 22576469
2018 INPP4B promotes cell survival via SGK3 activation in NPM1-mutated leukemia. Journal of experimental & clinical cancer research : CR 20 29343273
2015 Serum- and glucocorticoid-inducible kinase SGK2 regulates human organic anion transporters 4 via ubiquitin ligase Nedd4-2. Biochemical pharmacology 20 26740304
2019 Functional role of SGK3 in PI3K/Pten driven liver tumor development. BMC cancer 19 30975125
1999 Cloning and mapping of a novel human serum/glucocorticoid regulated kinase-like gene, SGKL, to chromosome 8q12.3-q13.1. Genomics 19 10585774
2014 Up-regulation of Kir2.1 (KCNJ2) by the serum & glucocorticoid inducible SGK3. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 17 24556932
2009 Akt2 and SGK3 are both determinants of postnatal hair follicle development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 19433625
2020 Serum- and glucocorticoid- inducible kinase 2, SGK2, is a novel autophagy regulator and modulates platinum drugs response in cancer cells. Oncogene 15 32848212
2019 Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44. The Biochemical journal 15 31665227
2018 Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3β/β-catenin signalling. Journal of experimental & clinical cancer research : CR 15 29940988
2023 The SGK3-Catalase antioxidant signaling axis drives cervical cancer growth and therapy resistance. Redox biology 13 37866161
2019 SGK2 promotes renal cancer progression via enhancing ERK 1/2 and AKT phosphorylation. European review for medical and pharmacological sciences 13 31002126
2015 SGK3 (CISK) may induce tumor angiogenesis (Hypothesis). Oncology letters 13 26170971
2025 N-acetyltransferase 10 impedes EZH2/H3K27me3/GABARAP axis mediated autophagy and facilitates lung cancer tumorigenesis through enhancing SGK2 mRNA acetylation. International journal of biological macromolecules 12 39814292
2020 Mutation of SGK3, a Novel Regulator of Renal Phosphate Transport, Causes Autosomal Dominant Hypophosphatemic Rickets. The Journal of clinical endocrinology and metabolism 12 31821448
2021 In vitro reconstitution of Sgk3 activation by phosphatidylinositol 3-phosphate. The Journal of biological chemistry 11 34181950
2018 Identification, structure modification, and characterization of potential small-molecule SGK3 inhibitors with novel scaffolds. Acta pharmacologica Sinica 11 30038340
2017 SGK2 promotes hepatocellular carcinoma progression and mediates GSK-3β/β-catenin signaling in HCC cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 11 28639896
2016 Serum- and glucocorticoid-inducible kinase sgk2 stimulates the transport activity of human organic anion transporters 1 by enhancing the stability of the transporter. International journal of biochemistry and molecular biology 11 27335683
2021 Complement C3a activates osteoclasts by regulating the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma. Cancer biology & medicine 10 33960177
2011 SGK3: a novel regulator of renal phosphate transport? Kidney international 10 21673735
2011 Novel role for SGK3 in glucose homeostasis revealed in SGK3/Akt2 double-null mice. Molecular endocrinology (Baltimore, Md.) 10 21980074
2019 A frameshift insertion in SGK3 leads to recessive hairlessness in Scottish Deerhounds: a candidate gene for human alopecia conditions. Human genetics 9 30927068
2019 MiR-376a functions as tumor suppressor by targeting SGK3 in renal cell carcinoma. European review for medical and pharmacological sciences 9 31114998
2018 The SGK3-triggered ubiquitin-proteasome degradation of podocalyxin (PC) and ezrin in podocytes was associated with the stability of the PC/ezrin complex. Cell death & disease 9 30385740
2006 Additive regulation of GluR1 by stargazin and serum- and glucocorticoid-inducible kinase isoform SGK3. Pflugers Archiv : European journal of physiology 9 16485113
2006 The critical roles of serum/glucocorticoid-regulated kinase 3 (SGK3) in the hair follicle morphogenesis and homeostasis: the allelic difference provides novel insights into hair follicle biology. The American journal of pathology 9 16565488
2024 SGK3 promotes vascular calcification via Pit-1 in chronic kidney disease. Theranostics 8 38169564
2022 CDK9 binds and activates SGK3 to promote cardiac repair after injury via the GSK-3β/β-catenin pathway. Frontiers in cardiovascular medicine 8 36082129
2021 Hsa-miR-100-3p Controls the Proliferation, DNA Synthesis, and Apoptosis of Human Sertoli Cells by Binding to SGK3. Frontiers in cell and developmental biology 8 34046405
2020 SGK2 is overexpressed in colon cancer and promotes epithelial-mesenchymal transition in colon cancer cells. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 8 32565024
2020 Oxymatrine inhibits the development of non-small cell lung cancer through miR-367-3p upregulation and target gene SGK3 downregulation. American journal of translational research 8 33042436
2024 SGK3 deficiency in macrophages suppresses angiotensin II-induced cardiac remodeling via regulating Ndufa13-mediated mitochondrial oxidative stress. Cellular and molecular life sciences : CMLS 7 39158709
2023 The role of the SGK3/TOPK signaling pathway in the transition from acute kidney injury to chronic kidney disease. Frontiers in pharmacology 7 37361201
2022 MicroRNA-92a-3p Regulates Retinal Angiogenesis by Targeting SGK3 in Vascular Endothelial Cells. Investigative ophthalmology & visual science 7 36269185
2021 SGK2, 14-3-3, and HUWE1 Cooperate to Control the Localization, Stability, and Function of the Oncoprotein PTOV1. Molecular cancer research : MCR 7 34654719
2022 Contributions of SGK3 to transporter-related diseases. Frontiers in cell and developmental biology 6 36531961
2016 SGK3 Sensitivity of Voltage Gated K+ Channel Kv1.5 (KCNA5). Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 6 26824455
2015 Lethality of PAK3 and SGK2 shRNAs to human papillomavirus positive cervical cancer cells is independent of PAK3 and SGK2 knockdown. PloS one 6 25615606
2010 Blunted IgE-mediated activation of mast cells in mice lacking the serum- and glucocorticoid-inducible kinase SGK3. American journal of physiology. Cell physiology 6 20686074
2004 A mutation in the serum and glucocorticoid-inducible kinase-like kinase (Sgkl) gene is associated with defective hair growth in mice. DNA research : an international journal for rapid publication of reports on genes and genomes 6 15871460
2015 Loss of serum and glucocorticoid-regulated kinase 3 (SGK3) does not affect proliferation and survival of multiple myeloma cell lines. PloS one 4 25837824
2010 Regulation of gastric acid secretion by the serum and glucocorticoid inducible kinase isoform SGK3. Journal of gastroenterology 4 21113728
2025 Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma. Journal of translational medicine 3 40091033
2021 Protein Kinase SGK2 Is Induced by the β3 Adrenergic Receptor-cAMP-PKA-PGC-1α/NT-PGC-1α Axis but Dispensable for Brown/Beige Adipose Tissue Thermogenesis. Frontiers in physiology 3 34899399
2020 Whole Genome Analysis of a Single Scottish Deerhound Dog Family Provides Independent Corroboration That a SGK3 Coding Variant Leads to Hairlessness. G3 (Bethesda, Md.) 3 31727632
2016 SGK3 Sensitivity of Large-Conductance Ca2+-Activated K+ Channel. Neuro-Signals 3 27898416
2025 The SGK3/GSK3β/β-catenin signaling promotes breast cancer stemness and confers resistance to alpelisib therapy. International journal of biological sciences 2 40303291
2025 SGK3 promotes estrogen receptor-positive breast cancer proliferation by activating STAT3/ZMIZ2 pathway to stabilise β-catenin. British journal of pharmacology 1 39876548
2020 Risk of Nasopharyngeal Carcinoma Associated with Single Nucleotide Polymorphisms in the MicroRNA Binding Site of SGK3. Genetic testing and molecular biomarkers 1 32644852
2026 Semaphorin 7A aggravates abdominal aortic aneurysm through PDK1/SGK3/YTHDC1 axis-mediated phenotypic switching of vascular smooth muscle cells. Cardiovascular research 0 41553434
2026 Inhibition of SGK3 regulates hyperplastic scar development in rats through the MAPK/ERK signaling pathway. Cell cycle (Georgetown, Tex.) 0 41674333
2026 SGK2 mediates apoptosis in herpes simplex keratitis by suppressing protective autophagy via the mTOR pathway. Virology journal 0 41851796
2026 Mll5 haploinsufficiency attenuates microglial phagocytosis through dysregulated TREM2-SGK3-GSK3β signaling and recapitulates ASD-like behaviors in mice. Nature communications 0 41997967