Ask about this productRelated genes to: DGKE antibody
- Gene:
- DGKE NIH gene
- Name:
- diacylglycerol kinase epsilon
- Previous symbol:
- -
- Synonyms:
- DAGK6, DGK
- Chromosome:
- 17q22
- Locus Type:
- gene with protein product
- Date approved:
- 1998-10-02
- Date modifiied:
- 2015-11-09
Related products to: DGKE antibody
Related articles to: DGKE antibody
- Complement dysregulation is a key mechanism underlying atypical hemolytic uremic syndrome and complement-mediated thrombotic microangiopathy in kidney transplantation, and is associated with post-transplant recurrence, graft dysfunction, and graft loss. Although Western cohort data are well established, integrated transplant outcome data combining genetic analysis, anti-factor H (AFH) antibody profiling, and individualized therapy from Indian and other South Asian populations remain limited, despite a distinct biologic profile in this region. - Source: PubMed
Balwani ManishPasari AmitKashiv PranjalRamteke VishalTolani PriyankaManuja NishthaKurundwadkar MohitDubey ShubhamPawar TwinkleMalde SunnyGupta SushrutSejpal KapilJeyachandran VijayKute Vivek B - Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting and persistent chronic inflammation, yet the multi-lineage cellular drivers of its pathogenesis remain incomplete. In this study, single-cell RNA sequencing (scRNA-seq) identified Atp6ap2 as a profoundly upregulated gene across multiple skeletal muscle cell types-particularly endothelial cells, fibroblasts, and myoblasts-in both mdx and severe mdx mice. Weighted gene co-expression network analysis (WGCNA) linked Atp6ap2 expression to DMD progression, while enrichment analyses revealed that its dysregulation severely impairs vascular homeostasis and extracellular matrix integrity via the PI3K-Akt, focal adhesion, and cell cycle pathways. Utilizing Connectivity Map (CMap) analysis, we identified temozolomide (TMZ) as a top pharmacological candidate capable of reversing the ATP6AP2-associated gene signature. In vivo validation demonstrated that TMZ administration significantly enhanced motor coordination, balance, and grip strength in mdx mice, while markedly preserving dystrophic muscle architecture, reducing myofiber necrosis, and alleviating interstitial fibrosis. Mechanistically, integrated transcriptomic and metabolomic profiling revealed that TMZ induced profound metabolic and signaling shifts, modulating the Notch, MAPK, and Ras pathways, as well as autophagy and glycerophospholipid metabolism. Furthermore, scRNA-seq and cell-cell communication analyses indicated that TMZ dynamically reorganized multicellular networks, decreasing aberrant fibroblast and endothelial interactions. Crucially, immunofluorescence and Western blot validations confirmed that TMZ drastically attenuated the infiltration of F4/80-positive macrophages and suppressed their pro-inflammatory M1 polarization (indicated by reduced co-localization with iNOS and ATP6AP2), while successfully reversing the dysregulation of the ATP6AP2 axis and restoring its downstream targets MAP4K2, DGKE, and EFNA1. Collectively, our findings demonstrate that TMZ mitigates dystrophic pathology by targeting the ATP6AP2 signaling axis and dampening macrophage-mediated inflammatory responses, highlighting its potential as a novel immunopharmacological therapeutic strategy for DMD. - Source: PubMed
Publication date: 2026/08/13
Zhou LinZhang YuTan XinxinTao LihongWu Xuan - EGFR is a key oncogenic driver of lung adenocarcinoma, and resistance to its tyrosine kinase inhibitors has become a major clinical challenge in the treatment of EGFR-mutated LUAD patients. Through preliminary experiments including Western blot and immunohistochemistry staining, RBM15 was identified as an oncogene promoting drug resistance in EGFR-mutant LUAD cell lines PC-9 and HCC827. Analysis of the TCGA-LUAD cohort revealed a positive correlation between RBM15 and EGFR expression, whereas RBM15 gain-of-function was negatively associated with LUAD patient survival. RBM15 expression was higher in EGFR-mutant LUAD cell lines PC-9 and HCC827 compared to non-EGFR-mutant cell line A549. Furthermore, RBM15 was downregulated in PC-9 and HCC827 cells following gefitinib treatment. Knockdown of RBM15 reduced proliferation and promoted apoptosis in PC-9 and HCC827 cells in vitro, while also inhibiting the growth of PC-9 xenograft tumors in mice. Notably, RBM15 overexpression rescued these effects and promoted gefitinib resistance in PC-9 and HCC827 cells. Transcriptomic and metabolomic sequencing analyses of RBM15-knockdown PC-9 cells revealed enrichment in multiple cancer signaling pathways, including mitochondrial fatty acid metabolism. Diacylglycerol kinase ε (DGKE) was identified as a novel interacting protein of RBM15, and RBM15 was found to influence fatty acid metabolism by modulating mitochondrial function. In summary, RBM15 promotes tumorigenic proliferation, suppresses apoptosis, and enhances gefitinib resistance in EGFR-mutant LUAD cells by regulating the EGFR signaling pathway and interacting with DGKE. Based on the interplay among RBM15, EGFR, and downstream DGKE, RBM15 may serve as a promising new therapeutic target for EGFR-mutant LUAD. - Source: PubMed
Publication date: 2026/07/09
Ma MingshengWang WeiWang XiaoyanZhao JieYang YantaoHe MengLu HongLuo NaJiang XintianYe Lianhua - Complement dysregulation is frequently implicated in the thrombotic microangiopathy (TMA) known as atypical hemolytic uremic syndrome (aHUS). Diacylglycerol kinase epsilon (DGKE) mutations encode a non-complement regulatory protein, and pathogenic variants in DGKE define a distinct form of aHUS. Indeed, the DGKEgene encodes a key enzyme involved in intracellular signaling. While eculizumab and other anti-C5 monoclonal antibodies are widely used in complement-related aHUS, their relevance in DGKE-associated forms remains controversial. We report a case of a patient followed from the age of eight months for suspected aHUS. Genetic testing, performed only at the age of 13 years, revealed a homozygous DGKE mutation (c.412T>C; p.C138R), despite a typical presentation, including hemolytic anemia, thrombocytopenia, and acute kidney injury. Due to severe disease progression and a fatal family history, empirical eculizumab therapy was initiated. Although the treatment resulted in a stable overall clinical status, relapses manifested as isolated nephrotic-range proteinuria (without hemolysis) on two occasions during treatment interruptions. Complement C3 levels remained consistently within the normal range. In this case, eculizumab did not prevent disease relapses, which occurred in the absence of complement activation. The persistence of proteinuria despite C5 blockade further highlights this distinction. The lack of genetic testing options has led to overtreatment in this patient with that type of mutation, with additional costs associated with the drug (eculizumab) and an increased risk of life-threatening infectious complications for the patient. - Source: PubMed
Publication date: 2026/03/31
Chelghoum SouadMesnard LaurentYousfi NadhirRostaing LionelKhellaf Ghalia - BACKGROUND: Diacylglycerol kinase-ε (DGKε) is a unique member of the DGK family with strict specificity toward SAG, stearic/palmitic and arachidonic fatty acid-containing DAG, which produces phosphatidic acid used for the synthesis of phosphatidylinositol (PI). PI and its derivatives orchestrate numerous processes. These include the pro-inflammatory signaling of Toll-like receptor 4 (TLR4) and its accessory protein, CD14, which are activated in macrophages by bacterial lipopolysaccharide (LPS). METHODS: To assess the role of DGKε in LPS-induced responses, we obtained Raw264.7 cells stably depleted of DGKε and subsequently rescued them with DGKε-Myc. The DGKε-depleted cells were also treated with a synthetic GPI precursor. To assess the activity of DGKε and other DGKs in cellular fractions, a fluorescent assay was used, followed by thin-layer chromatography. RT-qPCR, immunoblotting, ELISA, and flow cytometry were used to examine protein abundance, LPS-induced signaling, and cytokine production. Cytokine expression was also analyzed after TLR2 activation. Cells were fractionated with Triton X-100 and X-114 to examine the distribution of GPI-anchored proteins (GPI-APs). Dgke was silenced with siRNA in mouse bone marrow-derived macrophages (BMDM). RESULTS: SAG phosphorylation was markedly decreased in DGKε-depleted Raw264.7 cells, with the activity of other DGKs unaffected. The DGKε depletion abolished the endosomal TLR4 signaling, engaging TRIF and IRF3. The MyD88-dependent signaling pathway was partially inhibited. No mature, GPI-anchored form of CD14 was produced in the DGKε-depleted cells, and residual amounts of CD14 and other GPI-APs were found on the cell surface. The DGKε depletion also inhibited TLR2-mediated cytokine expression and reduced CD14 level in BMDM. The reintroduction of DGKε in Raw264.7 cells restored SAG phosphorylation, total and cell-surface abundance of GPI-CD14 and other GPI-APs, and TLR4 and TLR2 signaling. Treatment of cells with the synthetic GPI precursor partially restored the cell-surface level of CD14. CONCLUSIONS: DGKε-dependent phosphorylation of SAG controls the biosynthesis of the GPI moiety of CD14, thereby affecting TLR signaling in macrophages. In addition, DGKε can influence the TLR pathways independently of CD14 formation. Together, these findings identify DGKε as a key factor determining the sensitivity of macrophages to LPS and other microbial components. - Source: PubMed
Publication date: 2026/04/25
Hromada-Judycka AnetaTraczyk GabrielaBen Amor IchrakCiesielska AnnaMąkosa AnielaVaron Silva DanielKwiatkowska Katarzyna