DGKE

Last update 08 May 2025

Basic Info

Synonyms

DAG kinase epsilon, DAGK5, DAGK6

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Introduction

Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:15544348, PubMed:19744926, PubMed:21477596, PubMed:22108654, 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 (PubMed:15544348, PubMed:8626589). Also plays an important role in the biosynthesis of complex lipids (PubMed:8626589). Displays specificity for diacylglycerol substrates with an arachidonoyl acyl chain at the sn-2 position, with the highest activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol the main diacylglycerol intermediate within the phosphatidylinositol turnover cycle (PubMed:19744926, PubMed:22108654, PubMed:23274426). Can also phosphorylate diacylglycerol substrates with a linoleoyl acyl chain at the sn-2 position but much less efficiently (PubMed:22108654).

100 Clinical Results associated with DGKE

100 Translational Medicine associated with DGKE

0 Patents (Medical) associated with DGKE

Literatures (Medical) associated with DGKE

01 Mar 2024·Molecular Metabolism

Renal tubule-specific Atgl deletion links kidney lipid metabolism to glucagon-like peptide 1 and insulin secretion independent of renal inflammation or lipotoxicity

Article

Author: Marvyn, Phillip M ; St-Pierre, Philippe ; Joseph, Jamie W ; Nachbar, Renato ; M'Hiri, Iman ; Wiens, Meghan A ; Fernandes, Maria F ; Doucette, Christine A ; Hoang, Monica ; Duncan, Robin E ; Marette, André ; Diaguarachchige De Silva, Kalsha ; Sebastian, Manuel ; Stark, Ken D ; Aristizabal-Henao, Juan J ; Wood, Geoffrey A

OBJECTIVELipotoxic injury from renal lipid accumulation in obesity and type 2 diabetes (T2D) is implicated in associated kidney damage. However, models examining effects of renal ectopic lipid accumulation independent of obesity or T2D are lacking. We generated renal tubule-specific adipose triglyceride lipase knockout (RT-SAKO) mice to determine if this targeted triacylglycerol (TAG) over-storage affects glycemic control and kidney health.METHODSMale and female RT-SAKO mice and their control littermates were tested for changes in glycemic control at 10-12 and 16-18 weeks of age. Markers of kidney health and blood lipid and hormone concentrations were analyzed. Kidney and blood lysophosphatidic acid (LPA) levels were measured, and a role for LPA in mediating impaired glycemic control was evaluated using the LPA receptor 1/3 inhibitor Ki-16425.RESULTSAll groups remained insulin sensitive, but 16- to 18-week-old male RT-SAKO mice became glucose intolerant, without developing kidney inflammation or fibrosis. Rather, these mice displayed lower circulating insulin and glucagon-like peptide 1 (GLP-1) levels. Impaired first-phase glucose-stimulated insulin secretion was detected and restored by Exendin-4. Kidney and blood LPA levels were elevated in older male but not female RT-SAKO mice, associated with increased kidney diacylglycerol kinase epsilon. Inhibition of LPA-mediated signaling restored serum GLP-1 levels, first-phase insulin secretion, and glucose tolerance.CONCLUSIONSTAG over-storage alone is insufficient to cause renal tubule lipotoxicity. This work is the first to show that endogenously derived LPA modulates GLP-1 levels in vivo, demonstrating a new mechanism of kidney-gut-pancreas crosstalk to regulate insulin secretion and glucose homeostasis.

01 Mar 2024·Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

Interaction of ROMK2 channel with lipid kinases DGKE and AGK: Potential channel activation by localized anionic lipid synthesis

Article

Author: Możajew, Mariusz ; Filipek, Sławomir ; Krajewska, Milena ; Koprowski, Piotr

In this study, we utilized enzyme-catalyzed proximity labeling with the engineered promiscuous biotin ligase Turbo-ID to identify the proxisome of the ROMK2 channel. This channel resides in various cellular membrane compartments of the cell including the plasma membrane, endoplasmic reticulum and mitochondria. Within mitochondria, ROMK2 has been suggested as a pore-forming subunit of mitochondrial ATP-regulated potassium channel (mitoK_ATP). We found that ROMK2 proxisome in addition to previously known protein partners included two lipid kinases: acylglycerol kinase (AGK) and diacylglycerol kinase ε (DGKE), which are localized in mitochondria and the endoplasmic reticulum, respectively. Through co-immunoprecipitation, we confirmed that these two kinases are present in complexes with ROMK2 channels. Additionally, we found that the products of AGK and DGKE, lysophosphatidic acid (LPA) and phosphatidic acid (PA), stimulated the activity of ROMK2 channels in artificial lipid bilayers. Our molecular docking studies revealed the presence of acidic lipid binding sites in the ROMK2 channel, similar to those previously identified in Kir2 channels. Based on these findings, we propose a model wherein localized lipid synthesis, mediated by channel-bound lipid kinases, contributes to the regulation of ROMK2 activity within distinct intracellular compartments, such as mitochondria and the endoplasmic reticulum.

20 Jan 2024·Cureus

Novel Heterozygous Missense Variants in Diacylglycerol Kinase Epsilon and Complement Factor I: Potential Pathogenic Association With Atypical Hemolytic Uremic Syndrome

Author: Nester, Alex ; Abughanimeh, Omar K ; Baljevic, Muhamed

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA), which copresents with microangiopathic hemolytic anemia, thrombocytopenia, and kidney injury. While typical HUS is normally preceded by infections such as Shiga-toxin-producing Escherichia coli, atypical HUS (aHUS) has a genetic component that leads to dysregulation of the alternative complement pathway. We report a case of a 69-year-old female who developed aHUS after undergoing an elective knee surgery. Genetic testing revealed novel mutations affecting diacylglycerol kinase epsilon (DGKE) protein and complement factor I (CFI) that were not reported before as pathogenic. The patient was treated with eculizumab, leading to the complete resolution of TMA with no lasting organ damage.

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DGKE

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