Displays a strong preference for 1,2-diacylglycerols over 1,3-diacylglycerols, but lacks substrate specificity among molecular species of long chain diacylglycerols. Regulates RASGRP1 activity (By similarity). Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes. Activates PIP5K1A activity via generation of phosphatidic acid (PubMed:27739494).
Diacylglycerol kinases (DAGKs) catalyse ATP-dependent phosphorylation of sn-1,2-diacylglycerol that arises during stimulated phosphatidylinositol turnover. DAGKα is activated in vitro by Ca2+ and by acidic phospholipids. The regulatory region of DAGKα includes an N-terminal RVH motif and EF hands that mediate Ca2+-dependent activation. DAGKα also contains tandem C1 protein kinase C homology domains. We utilized yeast, Saccharomyces cerevisiae, which lacks an endogenous DAGK, to express DAGKα and to determine the enzymic activities of different mutant forms of pig DAGKα in vitro. Six aspartate residues conserved in all DAGKs were individually examined by site-directed mutagenesis. Five of these aspartate residues reside in conserved blocks that correspond to sequences in the catalytic site of phosphofructokinases. Mutation of D434 (Asp434) or D650 abolished all DAGKα activity, whereas substitution of one among D465, D497, D529 and D697 decreased the activity to 6% or less of that for ...
TY - JOUR. T1 - sn-1,2-diacylglycerol kinase of Escherichia coli. Structural and kinetic analysis of the lipid cofactor dependence. AU - Walsh, J. P.. AU - Bell, R. M.. PY - 1986/12/1. Y1 - 1986/12/1. N2 - The lipid cofactor requirement of Escherichia coli sn-1,2-diacylglycerol kinase was studied using a β-octylglucoside mixed micellar assay (Walsh, J.P., and Bell, R.M. (1986) J. Biol. Chem. 261, 6239-6247). The enzyme was shown to have an absolute requirement for a lipid activator. sn-1,2-Dioleoylglycerol was both an activator and a substrate for the enzyme, 1,3-dioleoylglycerol was an activator but not a substrate, and sn-1,2-dioctanoylglycerol was a substrate but not an activator. Activation was observed with a large number of phospholipids, sulfolipids, neutral lipids, and detergents. Lipids with longer alkyl/acyl chains stimulated activity to a greater extent and lower concentrations than their shorter chain homologs. Anionic lipids were the best activators, and neutral lipids were ...
BioAssay record AID 504420 submitted by The Scripps Research Institute Molecular Screening Center: Summary of the probe development efforts to identify inhibitors of human diacylglycerol lipase, beta (DAGLB).
TY - JOUR. T1 - Nuclear Diacylglycerol Kinase-θ is Activated in Response to α-Thrombin. AU - Bregoli, Lisa. AU - Baldassare, Joseph J.. AU - Raben, Daniel M.. PY - 2001/6/29. Y1 - 2001/6/29. N2 - Currently, there is substantial evidence that nuclear lipid metabolism plays a critical role in a number of signal transduction cascades. Previous work from our laboratory showed that stimulation of quiescent fibroblasts with α-thrombin leads to the production of two lipid second messengers in the nucleus: an increase in nuclear diacylglycerol mass and an activation of phospholipase D, which catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid. Diacylglycerol kinase (DGK) catalyzes the conversion of diacylglycerol to phosphatidic acid, making it an attractive candidate for a signal transduction component. There is substantial evidence that this activity is indeed regulated in a number of signaling cascades (reviewed by van Blitterswijk, W. J., and Houssa, B. (1999) Chem. ...
Diacylglycerol (DAG) is a critical second messenger that mediates T cell receptor (TCR)-stimulated signaling. The abundance of DAG is reduced by the diacylglycerol kinases (DGKs), which catalyze the conversion of DAG to phosphatidic acid (PA) and thus inhibit DAG-mediated signaling. In T cells, the predominant DGK isoforms are DGKα and DGKζ, and deletion of the genes encoding either isoform enhances DAG-mediated signaling. We found that DGKζ, but not DGKα, suppressed the development of natural regulatory T (Treg) cells and predominantly mediated Ras and Akt signaling downstream of the TCR. The differential functions of DGKα and DGKζ were not attributable to differences in protein abundance in T cells or in their localization to the contact sites between T cells and antigen-presenting cells. RasGRP1, a key DAG-mediated activator of Ras signaling, associated to a greater extent with DGKζ than with DGKα; however, in silico modeling of TCR-stimulated Ras activation suggested that a ...
... (DGK, EC 2.7.1.107) is a lipid kinase that phosphorylates diacylglycerol (DAG) to generate phosphatidic acid (PA). DGK belongs to a well-conserved family of proteins found in diverse species, such as Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, mammals, plants, and bacteria (Merida et al. Biochem J 409:1-18, 2008). In eukaryotes, DGK can be activated in response to various stimuli, and its product PA is emerging as a novel lipid second messenger (Munnik, Trends Plant Sci 6:227-233, 2001; Testerink and Munnik, Trends Plant Sci 10:368-375, 2005). Despite similarities to the mammalian system, plant DGKs display several distinctive features ...
in Journal of Molecular Biology (2008), 383(4), 797-809. The epsilon isoform of diacylglycerol kinase (DGKepsilon) is unique among mammalian DGKs in having a segment of hydrophobic amino acids comprising approximately residues 20 to 41. Several algorithms ... [more ▼]. The epsilon isoform of diacylglycerol kinase (DGKepsilon) is unique among mammalian DGKs in having a segment of hydrophobic amino acids comprising approximately residues 20 to 41. Several algorithms predict this segment to be a transmembrane (TM) helix. Using PepLook, we have performed an in silico analysis of the conformational preference of the segment in a hydrophobic environment comprising residues 18 to 42 of DGKepsilon. We find that there are two distinct groups of stable conformations, one corresponding to a straight helix that would traverse the membrane and the second corresponding to a bent helix that would enter and leave the same side of the membrane. Furthermore, the calculations predict that substituting the Pro32 ...
ABSTRACT. Diacylglycerol kinase (DGK) is an enzyme that converts diacylglycerol to phosphatidic acid. Several DGK isoforms have been implicated in the pathogenesis of seizure, but the role of DGKβ in seizure is unknown. In the present study, we investigated the involvement of DGKβ in seizure using DGKβ knockout (KO) mice. Seizures were more severe in DGKβ KO mice than in wild-type (WT) mice after pentylenetetrazol (PTZ) treatment and after kainic acid treatment, but there were no differences in latency to seizure. The expression levels of DGKβ in the hippocampal CA1, CA3, or DG areas did not differ between PTZ (60 mg/kg) treatment and saline treatment. There were fewer parvalbumin-positive interneurons in the hippocampal CA3 area in DGKβ KO mice than in control WT mice, which might partly account for the increased seizure susceptibility displayed by DGKβ KO mice. These results suggest that DGKβ may play a pivotal role in the development of the relevant interneurons, and that on inherent ...
This project is supported by the Canadian Institutes of Health Research, Canada Foundation for Innovation, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Canada, Genome Alberta, and Genome British Columbia, a not-for-profit organization that is leading Canadas national genomics strategy with $900 million in funding from the federal government ...
Recombinant full-length human DGKE was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag. Diacylglycerol kinase epsilon (DAG kinase epsilon) is the only member of class III diacylglycerol kinase family.
Microbial lipid production represents a potential alternative feedstock for the biofuel and oleochemical industries. Since Escherichia coli exhibits many genetic, technical, and biotechnological advantages over native oleaginous bacteria, we aimed to construct a metabolically engineered E. coli strain capable of accumulating high levels of triacylglycerol (TAG) and evaluate its neutral lipid productivity during high cell density fed-batch fermentations. The Streptomyces coelicolor TAG biosynthesis pathway, defined by the acyl-CoA:diacylglycerol acyltransferase (DGAT) Sco0958 and the phosphatidic acid phosphatase (PAP) Lppβ, was successfully reconstructed in an E. coli diacylglycerol kinase (dgkA) mutant strain. TAG production in this genetic background was optimized by increasing the levels of the TAG precursors, diacylglycerol and long-chain acyl-CoAs. For this we carried out a series of stepwise optimizations of the chassis by 1) fine-tuning the expression of the heterologous SCO0958 and lpp β genes
Diacylglycerol Kinase: An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
Dr. Fanani graduated from Biochemistry in 1996 at FCQ-UNC and began her doctoral studies under the direction of Dr. Bruno Maggio under the theme "Supramolecular modulation of the activity of sphingomyelinase in biointerphases", which ended in 2001 and for which he received the Dr. Agustin Marenzzi Prize, 2000/2001 awarded by the Faculty of Pharmacy and Biochemistry, Univ. Buenos Aires. She also developed a brief postdoctoral work following this subject in Dr. Maggio. During 2003-2005, she developed studied on "Lipid Modulation of the Diacylglycerol Kinase Activity of α - and γ -Isoforms" under the supervision of Dr. Richard Epand at McMaster University (Canada). After her return, she obtained a position as Assistant researched (2005) and then as Associate Researcher of CONICET (2008) at CIQUIBIC, focusing her studies on the interfacial restructuring suffering by lipid membranes when they are subjected to the action of lipolytic enzymes. In this way, she deepened in the study of the structural ...
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We describe the largest cohort of patients with DGKE nephropathy. The combined analysis of the ten newly identified cases with all previously published patients provides convincing evidence that this condition is a genetically and phenotypically distinct disease entity. However, the larger sample size has helped uncover findings that deviate from that of the original reports.. The predominant phenotype of DGKE nephropathy is early-onset relapsing HUS with chronic proteinuria and long-term progression to CKD. On the basis of the original report by Lemaire et al.5 and the reports that followed,7-10 DGKE-HUS appeared to be a disease with onset during early infancy. Aggregated data analysis show that indeed most patients with DGKE-HUS (86%) are diagnosed within the first year of life. However, there are now five patients diagnosed between the ages of 1 and 4 years. On that basis, it would be helpful to screen for DGKE mutations in all patients with aHUS, irrespective of age at diagnosis.. Chronic ...
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Diacylglycerol (DAG) influences numerous cell signaling cascades by functioning as an intracellular, allosteric activator of protein kinase C (PKC),…
Background: Activated PI3-Kinase Delta Syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). Objective: To review the clinical, immunological, histopathological and radiological features of APDS in a large genetically-defined international cohort. Methods: Clinical questionnaire, and review of medical notes, radiology histopathology and laboratory investigations of 53 APDS patients. Results: Recurrent sino-pulmonary infections (96%) and non-neoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system (CNS); consistent with this PI3Kδ is broadly expressed in the developing murine CNS. Thoracic ...
Begg M, Wilson R, Hamblin JN, Montembault M, Green J, Deans A, Amour A, Worsley S, Fantom K, Cui Y, Dear G, Ahmad S, Kielkowska A, Clark J, Boyce M, Cahn A, Hessel EM. Nemiralisib (GSK2269557) is a potent inhaled inhibitor of phosphoinositide 3-kinase delta (PI3Kδ) which is being developed for the treatment of respiratory disorders including COPD (Chronic Obstructive Pulmonary Disease). Determining the pharmacokinetic (PK) and pharmacodynamic (PD) responses of inhaled drugs early during drug development is key to informing the appropriate dose and preferred dose regimen in patients. We set out to measure PD changes in induced sputum in combination with drug concentrations in plasma and bronchoalveolar lavage (BAL) taken from healthy smokers (n=56) treated for up to 14 days with increasing doses of inhaled nemiralisib (0.1 mg to 6.4 mg). Induced sputum analysis demonstrated a dose-dependent reduction in phosphatidylinositol-trisphosphate (PIP3, the product of PI3K activation), with a maximum ...
STABLE PHARMACEUTICAL COMPOSITION COMPRISING PEMETREXED OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF | COMPOSITIONS AND METHODS FOR INHIBITION OF AUTOPHAGY | COMBINATION OF A 6-OXO-1,6-DIHYDRO-PYRIDAZINE DERIVATIVE HAVING ANTI-CANCER ACTIVITY WITH A QUINAZOLINE DERIVATIVE | Trk-INHIBITING COMPOUND | INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated ...
PRKCQ (pS676) Antibody is a Rabbit Polyclonal antibody against PRKCQ (pS676). Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members
Binding Sites, Cell, Cells, Diacylglycerol Kinase, Downregulation, Gene, Gene Expression, Il-2, Interleukin, Interleukin-2, Kinase, Luciferase, Mouse, Phosphatidic Acid, Phosphorylation, Proteins, Regulation, Regulatory Region, Role, T Cells
Monoklonale und polyklonale DGKA Antikörper für viele Methoden. Ausgesuchte Qualitäts-Hersteller für DGKA Antikörper. Hier bestellen.
Epidemiological and experimental studies suggest an inverse relationship between the intake of dietary selenium and/or low fat-intake and colon cancer risk. Efficacy studies in rodents suggest that the organoselenium compound 1, 4-phenylenebis(methylene)selenocyanate (p-XSC), is a more effective and less toxic chemopreventive agent than other organic or inorganic selenium compounds such as selenomethionine and Na2SeO3. The efficacy of p-XSC against colon cancer is significantly augmented by a low-fat diet. To explore the mechanisms by which this combined inhibiting effect against colon carcinogenesis comes about, we have investigated protein kinase C (PKC), tyrosine protein kinase (TPK), diacylglycerol kinase (DGK) activities and 8-isoprostane levels in colonic mucosa and tumor tissues in an azoxymethane (AOM)-induced rat colon cancer model. Weanling male F344 rats were fed the semipurified AIN-76A diet until seven weeks of age. Then various experimental groups were fed the low- or high-fat ...
This is the first report characterizing a functional role of DGKζ in the in vivo mouse heart. Molecular, gravimetric, and morphological analyses clearly showed that cardiac-specific overexpression of DGKζ abrogated cardiac hypertrophy in response to GPCR agonists such as angiotensin II and phenylephrine by regulating the DAG-PKC signaling in transgenic mouse hearts.. DGKζ-TG mice were indistinguishable in appearance from WT mice, and no baseline cardiac effects were observed in physiological or histological analyses. In addition, we found that isolated cardiomyocyte function and in vivo cardiac function evaluated by echocardiography were normal in DGKζ-TG mice. Blood pressure and heart rate after subcutaneous infusion of angiotensin II and phenylephrine were not different among DGKζ-TG-High, DGKζ-TG-Low, and WT mice, indicating that the overexpression of DGKζ does not affect hemodynamic regulations in response to angiotensin II and phenylephrine. Consistent with previous works,2,3,31,32 ...
Expression of DGKA (DAGK, DAGK1, DGK-alpha) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers.
Netherlands Institute for Neuroscience Bart Nieuwenhuis, Amanda C Barber, Rachel S Evans, Craig S Pearson, Joachim Fuchs, Amy R MacQueen, Susan van Erp, Barbara Haenzi, Lianne A Hulshof, Andrew Osborne, Raquel Conceicao, Tasneem Z Khatib, Sarita S Deshpande, Joshua Cave, Charles Ffrench-Constant, Patrice D Smith, Klaus Okkenhaug, Britta J Eickholt, Keith R Martin, James W Fawcett, Richard Eva PI 3-kinase delta enhances axonal PIP3 to support axon regeneration in the adult CNS EMBO Molecular Medicine 12 (2020) e11674 Download ...
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-3 is an enzyme that in humans is encoded by the PLCD3 gene. This gene encodes a member of the phospholipase C family, which catalyze the hydrolysis of phosphatidylinositol 4,5-bisphosphate to generate the second messengers diacylglycerol and inositol 1,4,5-trisphosphate (IP3). Diacylglycerol and IP3 mediate a variety of cellular responses to extracellular stimuli by inducing protein kinase C and increasing cytosolic Ca2+ concentrations. This enzyme localizes to the plasma membrane and requires calcium for activation. Its activity is inhibited by spermine, sphingosine, and several phospholipids. GRCh38: Ensembl release 89: ENSG00000161714 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000020937 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Kim H, Suh PG, Ryu SH, Park SH (Apr 2000). "Assignment of the human PLC delta3 gene (PLCD3) to human chromosome band 17q21 by fluorescence in situ ...
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription ...
In some cases, the inhibitory response outlasted the period of ANF application. Comparison of the Drosophila DGKepsilon with the human homologue revealed that the first zinc finger-like motif is specific for the type III isoform. From the Cz region of the human scalp, 2 components of potentials, early and late, were evoked following mechanical stimulation of a finger contralateral to the recording side. Two new species of the genus Zorochros (Coleoptera: Elateridae: Negastriinae) generic cialis 2019 from Korea. Egg yolk lecithin E80 and human serum albumin (HSA) were used as the main excipients to replace Cremophor EL in the commercial formulation.. CYP11B1 and CYP11B2 mRNA levels in APA are not related to the in vivo secretory activity of glomerulosa cells, where post-transcriptional factors might ultimately regulate aldosterone production. Compounds 1-3, 11 are new compounds never reported before and the promising results demonstrate the potential of compound 1-3, 9, 11, 12 for the buy generic ...
The use of chimeric antigen receptor (CAR)-redirected CD8+ T cells in the treatment of malignancy is a novel strategy that has shown tremendous promise; however, it remains likely this strategy could be enhanced when combined with additional approaches. We hypothesized that deletion of signaling mediators that negatively regulate TCR signal transduction might enhance CAR signaling and function, since CARs utilize the same machinery that transduces TCR signals. We tested CAR activity and function in T cells that lacked one or both lymphocyte-specific isoforms of diacylglycerol kinase (dgk), proteins that metabolize the second messenger DAG and limit Ras/ERK activation. We found that primary murine T cells transduced with CARs specific for the human tumor antigen mesothelin demonstrated greatly enhanced cytokine production and cytotoxicity when co-cultured with a murine mesothelioma line that stably expresses mesothelin. Additionally, we found that dgk-deficient CAR transduced T cells were more ...
TY - JOUR. T1 - Polarized THG Microscopy Identifies Compositionally Different Lipid Droplets in Mammalian Cells. AU - Bautista, Godofredo. AU - Pfisterer, Simon G.. AU - Huttunen, Mikko J.. AU - Ranjan, Sanjeev. AU - Kanerva, Kristiina. AU - Ikonen, Elina. AU - Kauranen, Martti. PY - 2014/11/18. Y1 - 2014/11/18. KW - MOLECULAR-STRUCTURE DETERMINATION. KW - INTEGRAL MEMBRANE-PROTEINS. KW - ERYTHROPOIETIN RECEPTOR. KW - TRANSMEMBRANE DOMAIN. KW - SIGNAL-TRANSDUCTION. KW - NMR-SPECTROSCOPY. KW - XPLOR-NIH. KW - DIACYLGLYCEROL KINASE. KW - DETERGENT MICELLES. KW - ACTIVATION. KW - 3111 Biomedicine. U2 - 10.1016/j.bpj.2014.10.009. DO - 10.1016/j.bpj.2014.10.009. M3 - Article. VL - 107. SP - 2230. EP - 2336. JO - Biophysical Journal. JF - Biophysical Journal. SN - 0006-3495. IS - 10. ER - ...
There is mounting evidence that most human genes show alternatively spliced isoforms, many of them regulated by tissue-specific factors. Indeed, alteration of alternative splicing is frequently linked to severe genetic diseases [17]. We report the characterization of 4 in-frame alternatively spliced isoforms of CERKL, which is responsible for an autosomal recessive form of retinitis pigmentosa (RP26). In our case, the isoform multiplicity increased the complexity of the functional analysis of a yet to be characterized lipid kinase. For instance, comparison of isoforms CERKLa and CERKLb revealed an additional exon (E4b), which introduces 26 additional amino acids in-frame within the DAG kinase catalytic domain and immediately upstream of the phosphate-donor binding site (GGDGS). The position of this exon in the presumptive catalytic domain makes it a good candidate for modulating the catalytic, substrate- or partner-binding abilities of the protein, as has been postulated for ...
Hypothetical scheme of the role of DGKζ in the regulation dendritic spine morphology. Based on Kim et al (this issue of EMBO J), the recruitment of DGKζ to th
Rabbit polyclonal DGKB antibody validated for WB, ELISA, IHC and tested in Human and Mouse. Immunogen corresponding to synthetic peptide
Affiliation:神戸大,助教授, Research Field:Pathological medical chemistry,General medical chemistry, Keywords:細胞内情報伝達,プロテインキナーゼC,Diacylglycerol,ホスホリパーゼA2,ホスホリパーゼD,ホスホリパーゼA_2,ジアシルグリセロール,ジアシルグリセロ-ル,Signal Transduction,プロテインキナ-ゼC, # of Research Projects:8, # of Research Products:0
GSK2269557 is potent and highly selective inhaled phosphoinositides 3-kinases -delta (PI3K-delta) inhibitor being developed as an anti-inflammatory agent for the treatment of inflammatory airway diseases. GSK2269557 has already been administered as a nebulized solution in single and repeat doses to humans and has been well tolerated across the range of doses used. The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of single and repeat inhaled doses of GSK2269557 as a dry powder. This study is the first administration of dry powder GSK2269557 in humans.. Part A will consist of four treatment periods separated by at least 14 days wash out periods. In each treatment period there will be 12 subjects receiving GSK2269557 and 4 subjects receiving placebo. The doses of GSK2269557 planned for Part A are 100 micrograms (mcg), 500 mcg and 3000 mcg. Blinded safety and available pharmacokinetic (PK) data will be reviewed before each dose escalation. Part B will be a ...
The small GTPase RHO-1 is an important regulator of neurotransmission. Caenorhabditis elegans nematodes expressing activated RHO-1 (G14V) in their cholinergic motor neurons (nRHO-1*) become hypersensitive to the acetylcholinesterase inhibitor aldicarb, demonstrating increased acetylcholine release, and acquire a highly loopy, uncoordinated locomotion. RHO-1 inhibits diacylglycerol kinase (DGK-1), and so increases the availability of diacylglycerol (DAG), a key second messenger for release at the presynaptic membrane. Inhibiting RHO-1 in a dgk-1 mutant causes a decrease in neurotransmitter release, demonstrating the presence of additional targets downstream of RHO-1. During a forward genetic screen for suppressors of the loopy locomotion of nRHO-1* animals we obtained a mutant, nz94, which carried an additional fainter phenotype, helping us identify it as an allele of unc-80, a large, conserved protein, important in the localization of NCA-1 and NCA-2, C. elegans homologues of the novel ...
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipid-dependent protein kinase. This kinase is important for T-cell activation. It is required for the activation of the transcription factors NF-kappaB and AP-1, and may link the T cell receptor (TCR) signaling complex to the activation of the transcription factors.[6]. ...
Protein kinase C (PKC) is a family of serine/threonine kinases consisting of at least 10 isoforms, including the classical PKCs (α, βI, βII, and γ), which bind to and are activated by diacylglycerol and Ca2+, the novel isoforms (δ, ε, η, and θ) capable of binding to diacylglycerol but independent of Ca2+, and the atypical class (ζ and ι) insensitive to either diacylglycerol or Ca2+. Most of these isozymes are regulated at 3 levels. First, autophosphorylation is required for them to become catalytically competent. Second, binding to cofactors, such as diacylglycerol or its mimetic phorbol esters, induces translocation from the cytosol to plasma membrane, where the enzymes undergo conformational changes enabling catalytic activation. Finally, direct interaction with substrate proteins determines site-specific kinase activities.1. As endogenous stress sensors, PKCs mediate diverse cellular responses to physical forces, chemical agents, and molecular signals that are elaborated under ...
Obesity in dogs and cats have been increasingly recognized in recent years. Because obesity underlies various diseases, pet owners and veterinarians have an important responsibility to help animals lose weight and maintain their health. But as in humans, losing weight is much more difficult than gaining weight. Is diacylglycerol a substance that helps solving this problem? It seems so!
Nuclei contain two differentially regulated pools of diacylglycerol.: A number of recent studies have highlighted the presence of a nuclear pool of inositol lip
Hyperglycemia and diabetes have been shown to increase diacylglycerol (DAG) level and activate protein kinase C (PKC) activity in the vascular tissues, possibly altering vascular function. We have characterized the effects of D-α-tocopherol (vitamin E) on PKC activities and DAG levels in rat aortic smooth muscle cells (ASMCs) cultured with elevated glucose levels as well as in the vascular tissues obtained from control and diabetic rats. In ASMCs, the specific PKC activity from the membraneous fraction and total DAG level were increased by 31 ± 4% (P , 0.05) and 50 ± 7% (P , 0.05), respectively, when the glucose levels were changed from 5.5 to 22 mmol/1. The addition of D-α-tocopherol and another lipophilic antioxidant, probucol, prevented the glucose-stimulated increases in DAG level and PKC activity. By immunoblotting studies, D-α-tocopherol treatment was able to reduce the enhancement of PKC (ill isoform in the membraneous fraction isolated from ASMCs. Comparing streptozotocin-induced ...
Synthesis of diacylglycerol begins with glycerol-3-phosphate, which is derived primarily from dihydroxyacetone phosphate, a product of glycolysis (usually in the cytoplasm of liver or adipose tissue cells). Glycerol-3-phosphate is first acylated with acyl-coenzyme A (acyl-CoA) to form lysophosphatidic acid, which is then acylated with another molecule of acyl-CoA to yield phosphatidic acid. Phosphatidic acid is then de-phosphorylated to form diacylglycerol. Dietary fat is mainly composed of triglycerides. Because triglycerides cannot be absorbed by the digestive system, triglycerides must first be enzymatically digested into monoacylglycerol, diacylglycerol, or free fatty acids.(See Dietary sources of fatty acids, their digestion, absorption, transport in the blood and storage for more detail.) Diacylglycerol is a precursor to triacylglycerol (triglyceride), which is formed in the addition of a third fatty acid to the diacylglycerol under the catalysis of diglyceride acyltransferase. Since ...
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An increasing number of reports are indicating key roles for DGKα in cancer. Although normally DGKα is significantly expressed only in brain, kidney, and T cells (14), it appears to be relevant in numerous malignancies. One of the earliest studies on DGKα in cancer notes DGKα overexpression and promotion of NF-κB signaling in melanoma cells (13). A few reports have linked DGKα to cancer cell motility; one report implicates DGKα in cancer cell invasion through α5β1 integrin recycling (RCP; ref. 15). Dominguez and colleagues (16) studied DGKα as a cancer target in vitro and in vivo. DGKα was identified as a potential cancer target through the study of tumor-suppressive microRNAs. After observing that microRNA-297 had tumor-suppressive function and was cytotoxic to glioblastoma cells, it was noted that its top predicted targets in online databases did not include established oncogenes (17). However, the kinase DGKα was predicted to be strongly targeted, and there were suggestions in the ...
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