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Last update 08 May 2025

SGK3

Last update 08 May 2025

Basic Info

Synonyms

CISK, Cytokine-independent survival kinase, Serine/threonine-protein kinase Sgk3

+ [8]

Introduction

Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. Up-regulates Na(+) channels: SCNN1A/ENAC and SCN5A, K(+) channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.

Drugs associated with SGK3

SGK3-PROTAC1

Target

SGK3

Mechanism

SGK3 inhibitors [+1]

Active Org.

University Of Dundee [+1]

Originator Org.

University Of Dundee

Active Indication

Breast Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DAT4 (University of Dundee)

Target

SGK3

Mechanism

SGK3 inhibitors

Active Org.-

Originator Org.

University Of Dundee

Active Indication-

Inactive Indication

Breast Cancer

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DAT12 (University of Dundee)

Target

SGK3

Mechanism

SGK3 inhibitors

Active Org.-

Originator Org.

University Of Dundee

Active Indication-

Inactive Indication

Breast Cancer

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with SGK3

100 Translational Medicine associated with SGK3

0 Patents (Medical) associated with SGK3

213

Literatures (Medical) associated with SGK3

01 Apr 2025·British Journal of Pharmacology

SGK3 promotes estrogen receptor‐positive breast cancer proliferation by activating STAT3/ZMIZ2 pathway to stabilise β‐catenin

Article

Author: Cai, Yongqing ; Yuan, Lie ; Liu, Xu ; Zhou, Weiying ; Qu, Na ; Li, Xiaoli ; Zhou, Duanfang ; Wu, Yuanli ; Chen, Bo ; Wang, Gang

Background and PurposeBreast cancer is a leading threat to women's health, with approximately 70% of cases being estrogen receptor‐positive. SGK3 is regulated by estrogen and is positively associated with estrogen receptor expression, although its molecular role remains unclear.Experimental ApproachProteomics was used to identify SGK3's downstream targets. Tissue microarray immunofluorescence evaluated SGK3 and ZMIZ2 expression in ER+ breast cancer. Lentiviral‐mediated knockdown and overexpression of SGK3 and/or ZMIZ2 assessed their effects on cell proliferation in vitro and in vivo. Chromatin immunoprecipitation (ChIP) analyzed p‐STAT3 binding to the ZMIZ2 promoter, and Co‐immunoprecipitation (Co‐IP) examined ZMIZ2‐β‐catenin interaction.Key ResultsSGK3 expression was elevated in breast tumour tissues correlating with reduced patient survival. Proteomic analysis identified ZMIZ2 as a downstream target of SGK3. Overexpression of SGK3 promoted the proliferation of estrogen receptor‐positive breast cancer in MCF‐7 and T47D cells. Inhibition had the opposite effects. ZMIZ2 overexpression rescued the proliferation deficit in SGK3 knockdown cells. ZMIZ2 was found to bind and stabilises β‐catenin. Knockdown of SGK3 led to β‐catenin degradation via polyubiquitination, a process reversed by ZMIZ2 overexpression. STAT3 was identified as a downstream effector of SGK3 and its knockdown reduced cytoplasmic and nuclear p‐STAT3 and STAT3, and inhibited ZMIZ2 and β‐catenin expression. Celastrol suppressed estrogen receptor‐positive breast cancer cell proliferation by inhibiting the SGK3/STAT3/ZMIZ2/β‐catenin pathway.Conclusions and ImplicationsSGK3 expression is associated with poorer survival rates, thus SGK3 is a potential therapeutic target. As celastrol can inhibit SGK3 expression it could be an effective therapeutic agent.

01 Jan 2025·Alternative therapies in health and medicine

Comparing Effects of Aerobic Versus Resistance Exercise on Expression of MicroRNA-155, Serum- and Glucocorticoid-Regulated Kinase 3, and Pain Threshold in Mice with Experimental Autoimmune Encephalomyelitis.

Article

Author: Kakavandi, Mina Ahmadi ; Shahrbanian, Shahnaz ; Kordi, Mohammad Reza ; Soltani, Bahram Mohammad

ObjectivesMultiple sclerosis is a complex neurological disorder in which the immune system attacks the myelin sheath, leading to a range of symptoms. microRNA-155 plays a significant role in the pathogenesis of multiple sclerosis and neuropathic pain. Serum- and glucocorticoid-regulated kinase 3 (SGK3) protein is the target of microRNA-155. Exercise can induce long-term changes in the expression of microRNAs and their target proteins. This study aims to compare the effects of resistance and aerobic exercises on the expression of microRNA-155, SGK3, and pain threshold in experimental autoimmune encephalomyelitis mice.MethodsFor this purpose, 24 female C57BL6 mice were divided into four groups using a simple random sampling method: healthy, experimental autoimmune encephalomyelitis, resistance exercise + experimental autoimmune encephalomyelitis, and aerobic exercise + experimental autoimmune encephalomyelitis. The exercise groups underwent four weeks of training, consisting of 5 sessions of 30 minutes per week. The expression of microRNA-155, SGK3 protein, and pain threshold were assessed using the real-time polymerase chain reaction method, Western blot analysis, and the tail flick test, respectively.ResultsThe results indicated significant changes in the expression of microRNA-155 (F = 22.05, P = .0003), SGK3 (F = 26.70, P = .0002), and pain threshold (F = 5.05, P = .009). Both resistance and aerobic exercises significantly down-regulated microRNA-155 and increased the expression of SGK3 compared to the experimental autoimmune encephalomyelitis control group (P < .05). The pain threshold in the mice also increased in both exercise groups (P < .05). No significant differences were observed between the resistance and aerobic exercise groups in any outcomes (P > .05).ConclusionExercise training, through its impact on epigenetic factors, may serve as an effective therapeutic intervention to alleviate pain in individuals with multiple sclerosis and could significantly manage disease symptoms.

01 Dec 2024·Cellular and Molecular Life Sciences

SGK3 deficiency in macrophages suppresses angiotensin II–induced cardiac remodeling via regulating Ndufa13–mediated mitochondrial oxidative stress

Article

Author: Qu, Peng ; Che, Yilin ; Ren, Jiayu ; Wang, Ying ; Wang, Yue ; Li, Heyu ; Li, Jing ; Su, Hongtong ; Gao, Haijun ; Li, Zhihan

Infiltration of monocyte-derived macrophages plays a crucial role in cardiac remodeling and dysfunction. The serum and glucocorticoid-inducible protein kinase 3 (SGK3) is a downstream factor of PI3K signaling, regulating various biological processes via an AKT-independent signaling pathway. SGK3 has been implicated in cardiac remodeling. However, the contribution of macrophagic SGK3 to hypertensive cardiac remodeling remains unclear. A cardiac remodeling model was established by angiotensin II (Ang II) infusion in SGK3-Lyz2-CRE (f/f, +) and wild-type mice to assess the function of macrophagic SGK3. Additionally, a co-culture system of SGK3-deficient or wild-type macrophages and neonatal rat cardiomyocytes (CMs) or neonatal rat fibroblasts (CFs) was established to evaluate the effects of SGK3 and the underlying mechanisms. SGK3 levels were significantly elevated in both peripheral blood mononuclear cells and serum from patients with heart failure. Macrophage SGK3 deficiency attenuated Ang II-induced macrophage infiltration, myocardial hypertrophy, myocardial fibrosis, and mitochondrial oxidative stress. RNA sequencing suggested Ndufa13 as the candidate gene in the effect of SGK3 on Ang II-induced cardiac remolding. Downregulation of Ndufa13 in CMs and CFs prevented the suppression of cardiac remodeling caused by SGK3 deficiency in macrophages. Mechanistically, the absence of SGK3 led to a reduction in IL-1β secretion by inhibiting the NLRP3/Caspase-1/IL-1β pathway in macrophages, consequently suppressing upregulated Ndufa13 expression and mitochondrial oxidative stress in CMs and CFs. This study provides new evidence that SGK3 is a potent contributor to the pathogenesis of hypertensive cardiac remodeling, and targeting SGK3 in macrophages may serve as a potential therapy for cardiac remodeling.

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SGK3

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