Disease relevance of DGKQ

• DAGK with an I110P or I110R mutation in the third transmembrane helix could not be purified because its expression was toxic to the E. coli host, most likely because of severe folding defects [1].
• The present results show that the DAG kinase inhibitor, R 59022, suppressed tumor cell polarity and strongly inhibited cell locomotion at a concentration of 10(-4), thus supporting the earlier finding that an increased availability of DAGs can suppress the locomotor activity of Walker carcinosarcoma cells [2].

High impact information on DGKQ

• Surprisingly, many commonly available human RhoA constructs contain an uncharacterized mutation that severely reduces binding of RhoA to DAG kinase [3].
• In one, presynaptic Rho increases acetylcholine (ACh) release by stimulating the accumulation of diacylglycerol (DAG) and the DAG-binding protein UNC-13 at sites of neurotransmitter release; this pathway requires binding of Rho to the DAG kinase DGK-1 [3].
• Translocation of diacylglycerol kinase theta from cytosol to plasma membrane in response to activation of G protein-coupled receptors and protein kinase C [4].
• Taken together, these data are the first to demonstrate an agonist-induced activity of nuclear DGK-theta activity and a nuclear localization of DGK-delta [5].
• We may speculate that nuclear speckle-located DGK-theta, on cell stimulation with an agonist, converts to PA the DAG derived from PLCbeta1-dependent PIP(2) hydrolysis [6].

Chemical compound and disease context of DGKQ

• Escherichia coli diacylglycerol kinase (DAGK) is a homotrimeric helical integral membrane protein in which a number of single-site mutations to cysteine are known to promote misfolding [1].

Biological context of DGKQ

• Assignment of the human diacylglycerol kinase 4 (DAGK4) gene to chromosome 4p16.3 [7].
• Structure-activity relationship of diacylglycerol kinase theta [8].
• When cells transfected with the p3TP-Lux reporter plasmid are simultaneously treated with TGF-beta and a DAG kinase inhibitor, we observed a higher level of luciferase than with TGF-beta alone [9].

Anatomical context of DGKQ

• Western blots demonstrated that DGK-theta was enriched in the nuclear matrix fraction prepared from MDA-MB-453 cells [6].
• Cell fractionation experiments performed in MDA-MB-453, HeLa, and PC12 cells showed a preferential association of DGK-theta with the nucleus [6].
• Here, we show, by immunofluorescence staining and confocal analysis, that DGK-theta localizes mainly to the nucleus of various cell lines, such as MDA-MB-453, MCF-7, PC12, and HeLa [6].
• The mechanism by which insulin increases diacylglycerol kinase (DAGK) activity has been studied in cerebral cortex (CC) synaptosomes from adult (3-4 months of age) rats [10].
• We thus investigated the involvement of a DAG kinase in several events subsequent to the activation of Jurkat T cells by CD3 mAb or phytohemagglutinin (PHA) [11].

Associations of DGKQ with chemical compounds

• Nuclear DGK-theta co-localizes with phosphatidylinositol 4,5-bisphosphate (PIP(2)) in domains that correspond to nuclear speckles, as revealed by the use of an antibody to the splicing factor SC-35, a well-established marker for these structures [6].
• Here, effects of other amino acid replacements have been explored using a folding assay based on the dilution of acidic urea/DAGK stock solutions into detergent/lipid mixed micelles [1].
• ADH also increased the prostaglandin E (PGE) secretion into serosal medium 3.5-fold and the release of arachidonic acid (AA) from 1,2-DAG, which was intensified in the presence of DAG kinase inhibitor R59022 [12].
• Phosphatidic acid, a product of DAG kinase, had no effect on TREK-2 [13].
• DiC8 (1,2-dioctanoyl-sn-glycerol, C8:0, Sigma Chemical Co., St. Louis, MO) induced spreading but only if DAG kinase inhibitor and A-23187 were also present; in their absence cells adhered but did not spread [14].

Other interactions of DGKQ

• DGK zeta (type IV) and DGK theta (type V) contain four tandem ankyrin repeats and a Ras-associating domain, respectively [15].
• Recently, a protein that is significantly similar to human DGK-theta, DGKA, was identified in Dictyostelium discoideum [16].

Analytical, diagnostic and therapeutic context of DGKQ

• Immunoprecipitation experiments with an antibody to PLCbeta1 revealed in MDA-MB-453 cells an association between this enzyme and both DGK-theta and phosphatidylinositol phosphate kinase Ialpha (PIPKIalpha) [6].

References