Last update 01 Nov 2024

DGKK

Last update 01 Nov 2024

Basic Info

Synonyms

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

+ [3]

Introduction

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).

Drugs associated with DGKK

FXS-01

Target

DGKK

Mechanism

DGKK stimulants [+1]

Active Org.-

Originator Org.

Lysogene SA

Active Indication-

Inactive Indication

Fragile X Syndrome

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with DGKK

100 Translational Medicine associated with DGKK

0 Patents (Medical) associated with DGKK

Literatures (Medical) associated with DGKK

01 Nov 2024·Animal Bioscience

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

Article

Author: 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.

01 Aug 2022·Biomaterials Advances

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

Article

Author: 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.

09 May 2022·EMBO Molecular MedicineQ1 · MEDICINE

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

Q1 · MEDICINE

ArticleOA

Author: 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.

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