更新于：2024-11-01

DGKK

更新于：2024-11-01

基本信息

别名

142 kDa diacylglycerol kinase、DAG kinase kappa、DGK-kappa

+ [3]

简介

Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:16210324, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable).

关联

项与 DGKK 相关的药物

FXS-01

靶点

DGKK

作用机制

DGKK刺激剂 [+1]

在研机构-

原研机构

Lysogene SA

在研适应症-

非在研适应症

脆性X综合征

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 DGKK 相关的临床结果

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100 项与 DGKK 相关的转化医学

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0 项与 DGKK 相关的专利（医药）

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项与 DGKK 相关的文献（医药）

2024-11-01·Animal Bioscience

Immunisation of the somatostatin gene alters hypothalamic-pituitary-liver gene expressions and enhances growth in Dazu black goats

Article

作者: Song, Xianqing ; Huang, Yongfu ; Han, Yanguo ; Zhang, Li ; Fang, Shiyong ; Qin, Ge ; Huang, Jiazhuo

Objective: Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the mechanism by which SS regulates growth and development in goats is still unclear.Methods: In this study, we randomly selected eight 7-month-old Dazu black goats (DBGs) of similar body weight and equally assigned four bucks as the immunised and negative control groups. The immunised group received the Salmonella typhi attenuated vaccine X9241 (ptCS/2SS-asd) orally, whilst the negative control group received the empty vector vaccine X9241 (pVAX-asd) orally.Results: The SS concentration in the serum of goats in the immunised group was significantly lower than that in the negative control group, and the daily gain was significantly higher (p<0.05). SS-14 DNA vaccine immunisation resulted in significantly higher concentrations of growth-related hormones such as GH-releasing hormone and insulin growth factor 1 (IGF-1) in the serum of goats (p<0.05). RNA-seq analysis of hypothalamus of oral SS-14 DNA vaccine and negative control DBGs identified 31 differentially expressed genes (DEGs). Pituitary gland identified 164 DEGs. A total of 246 DEGs were detected in the liver by RNA-seq. Gene ontology of DEGs was enriched in mitochondrial envelope, extracellular region, receptor binding and cell proliferation. The biological metabolic pathways associated with DEGs were explored by Kyoto encyclopedia of genes and genomes analysis. DEGs were associated with metabolic pathways, oxidative phosphorylation, vitamin digestion and absorption and galactose metabolism. These candidate genes (e.g. DGKK, CYTB, DUSP1, and LRAT) may provide references for exploring the molecular mechanisms by which SS promotes growth and development.Conclusion: Overall, these results demonstrated that the SS DNA vaccine enhanced the growth of DBGs by altering growth-related hormone concentrations and regulating the expression of growth-related genes in the hypothalamic–pituitary–liver axis.

2022-08-01·Biomaterials Advances

The generation of a lactate-rich environment stimulates cell cycle progression and modulates gene expression on neonatal and hiPSC-derived cardiomyocytes

Article

作者: Ball, Kristen ; Aguirre, Aitor ; Pérez-Amodio, Soledad ; Ordoño, Jesús ; Engel, Elisabeth

In situ tissue engineering strategies are a promising approach to activate the endogenous regenerative potential of the cardiac tissue helping the heart to heal itself after an injury. However, the current use of complex reprogramming vectors for the activation of reparative pathways challenges the easy translation of these therapies into the clinic. Here, we evaluated the response of mouse neonatal and human induced pluripotent stem cell-derived cardiomyocytes to the presence of exogenous lactate, thus mimicking the metabolic environment of the fetal heart. An increase in cardiomyocyte cell cycle activity was observed in the presence of lactate, as determined through Ki67 and Aurora-B kinase. Gene expression and RNA-sequencing data revealed that cardiomyocytes incubated with lactate showed upregulation of BMP10, LIN28 or TCIM in tandem with downregulation of GRIK1 or DGKK among others. Lactate also demonstrated a capability to modulate the production of inflammatory cytokines on cardiac fibroblasts, reducing the production of Fas, Fraktalkine or IL-12p40, while stimulating IL-13 and SDF1a. In addition, the generation of a lactate-rich environment improved ex vivo neonatal heart culture, by affecting the contractile activity and sarcomeric structures and inhibiting epicardial cell spreading. Our results also suggested a common link between the effect of lactate and the activation of hypoxia signaling pathways. These findings support a novel use of lactate in cardiac tissue engineering, modulating the metabolic environment of the heart and thus paving the way to the development of lactate-releasing platforms for in situ cardiac regeneration.

2022-05-09·EMBO Molecular Medicine1区 · 医学

AAV‐delivered diacylglycerol kinase DGKk achieves long‐term rescue of fragile X syndrome mouse model

1区 · 医学

ArticleOA

作者: Dembele, Doulaye ; Piguet, Françoise ; Laufer, Ralph ; Moine, Hervé ; Tabet, Ricardos ; Zámbó, Boglárka ; Habbas, Karima ; Riet, Fabrice ; Cakil, Oktay ; Hocquemiller, Michaël ; Mandel, Jean‐Louis

Fragile X syndrome (FXS) is the most frequent form of familial intellectual disability. FXS results from the lack of the RNA-binding protein FMRP and is associated with the deregulation of signaling pathways downstream of mGluRI receptors and upstream of mRNA translation. We previously found that diacylglycerol kinase kappa (DGKk), a main mRNA target of FMRP in cortical neurons and a master regulator of lipid signaling, is downregulated in the absence of FMRP in the brain of Fmr1-KO mouse model. Here we show that adeno-associated viral vector delivery of a modified and FMRP-independent form of DGKk corrects abnormal cerebral diacylglycerol/phosphatidic acid homeostasis and FXS-relevant behavioral phenotypes in the Fmr1-KO mouse. Our data suggest that DGKk is an important factor in FXS pathogenesis and provide preclinical proof of concept that its replacement could be a viable therapeutic strategy in FXS.