Diacylglycerol Production Research Articles

Diacylglycerol synthesis by lipase-catalyzed partial hydrolysis of palm oil under microwave irradiation and continuous flow conditions

Abstract Diacylglycerols (DAG) are commonly used in different purity levels for food, medicine and cosmetic industries. Several approaches are found over the literature on DAG production under lipase-catalyzed reactions among which are highlighted: glycerol sterification, vegetable oils’ glycerolysis and selective hydrolysis. Results obtained palm oil partial hydrolysis catalyzed by PS Amano IM under microwave irradiation show that DAG can be produced through short-term reactions and moderated yields (5 min, 30%). The DAG production using packed bed reactors under conventional heating and continuous flow conditions is more efficient allowing us to produce 128 g in 24 h with flow rate as a key feature.

Roles for class IIA phosphatidylinositol transfer protein in neurotransmission and behavioral plasticity at the sensory neuron synapses of Caenorhabditis elegans

Growing evidence suggests that sensory neuron synapses not merely pass, but actively encode sensory information and convey it to the central nervous system. The chemosensory preferences of Caenorhabditis elegans, as manifested in the direction of chemotaxis, are reversibly regulated by prior experience at the level of sensory neurons; the attractive drive is promoted by diacylglycerol (DAG) signaling, whereas the counteracting repulsive drive requires PtdIns(3,4,5)P(3) signaling. Here we report that the two opposing drives require a class IIA phosphatidylinositol transfer protein (PITP), PITP-1, which localizes to the sensory neuron synapses. In pitp-1 mutants, attraction behavior to salt is reduced, whereas conditioned repulsion from salt is eliminated: the mutants inflexibly show weak attraction behavior to salt, irrespective of prior experience. To generate flexible behavioral outputs, attraction and repulsion, PITP-1 acts in the gustatory neuron ASER and likely regulates neurotransmission from ASER, as pitp-1 mutations do not affect the ASER Ca(2+) response to sensory stimulus. Furthermore, full attraction to salt is restored in pitp-1 mutants by expression of the phosphatidylinositol transfer domain alone, and also by mutations of a DGK gene that cause accumulation of DAG, suggesting that PITP-1 serves for DAG production via phosphatidylinositol transport and, hence, regulates synaptic transmission. In addition to gustatory behavior, olfactory behaviors and osmotic avoidance are also regulated by PITP-1 in the sensory neurons that detect each sensory stimulus. Thus, PITP-1-dependent phosphatidylinositol transport is essential for sensory neuron synapses to couple sensory inputs to effective behavioral responses.

Effects of various ginseng saponins on 5-hydroxytryptamine release and aggregation in human platelets.

The effects of various ginseng saponins isolated from red ginseng roots, on aggregation and 5-hydroxytryptamine release (5-HT) human platelets have been investigated. Among the six saponins tested, only ginsenoside Rg1 inhibited adrenaline- and thrombin-induced platelet aggregation and 5-HT release dose-dependently, at concentrations of 5 to 500 micrograms ML-1. Ginsenoside Rg1 had no effect on adrenaline- and thrombin-induced arachidonic acid release and diacylglycerol production. But it did reduce the elevation of cytosolic free calcium concentration (Ca2+)i shown in the second phase induced by adrenaline and thrombin, at concentrations of 10 to 500 micrograms mL-1. Those data suggest that the inhibitory effects of ginsenoside Rg1 on 5-HT release from, and aggregation of, platelets might be due to the reduction of (Ca2+)i elevation at the second phase induced by adrenaline and thrombin. The results suggest that ginsenoside Rg1 in red ginseng roots may be active as a drug in the treatment of artheroscleorosis and thrombosis.

PLCε‐dependent activation of TRPC6 channels in kidney podocytes, murine embryonic fibroblasts (MEFs) and human embryonic kidney cells (HEK 293): A general mechanism?

Gain of function mutations of TRPC6 as well as loss of function mutations in PLC ε were identified in patients suffering from focal segmental glomerular sclerosis (FSGS), a disease displaying increasing proteinuria due to a defect in the glomerular filtration process of the kidney. Along these lines, we have previously shown that PLC ε physically interacts and activates TRPC6 via production of diacylglycerol (DAG) in kidney podocytes to increase the barrier function of the glomerular slit diaphragm. Moreover, down‐regulation of G‐protein α13‐subunits significantly reduced ATII‐mediated TRPC6 activation, whereas siRNAs directed against G protein αq‐subunits did not. By employing Gαq−/− murine embryonic fibroblasts, we were able to dissect Gα12/13‐PLC ε‐mediated from Gαq‐PLCβ‐induced TRPC6 activation using lysophosphatidic acid (LPA) receptor stimulation. Most interestingly, application of LPA resulted in a significantly larger increase in the intracellular Ca2+ concentration ([Ca2+]i) in Gαq−/− cells expressing TRPC6 in comparison to Gαq−/− control cells. Therefore, Gα12/13‐mediated activation of PLC ε via RhoA leading to TRPC6‐induced cation influx might be a general, but commonly‐ignored signal transduction pathway in many cell types.

PKD Regulates Membrane Fission to Generate TGN to Cell Surface Transport Carriers

The serine/threonine protein kinase D (PKD) is recruited to the trans-Golgi network (TGN) by binding diacylglycerol (DAG) and the ARF1 GTPase. PKD, at the TGN, promotes the production of phosphatidylinositol-4 phosphate (PI4P) by activating the lipid kinase phophatidylinositol 4-kinase IIIß (PI4KIIIß). PI4P recruits proteins such as oxysterol-binding protein 1 (OSBP) and ceramide transport protein (CERT) that control sphingolipid and sterol levels at the TGN. CERT mediated transport of ceramide to the TGN, we suggest, is used for increasing the local production and concentration of DAG. Once the crucial concentration of DAG is achieved, OSBP and CERT dissociate from the TGN on phosphorylation by PKD and DAG is sequentially converted into phosphatidic acid (PA) and lyso-PA (LPA). Therefore, the net effect of the activated PKD at the TGN is the sequential production of the modified lipids DAG, PA, and LPA that are necessary for membrane fission to generate cell surface specific transport carriers.

Native high-density lipoproteins inhibit platelet activation via scavenger receptor BI: Role of negatively charged phospholipids

ObjectivesHIGH-density lipoproteins (HDL) are a negative predictor of platelet-dependent thrombus formation and reduced platelet activation has been observed in vitro in the presence of HDL3, a major HDL fraction. However, mechanisms underlying the anti-thrombotic effects of HDL3 are poorly understood. Scavenger receptors class B represent possible HDL3 binding partners on platelets. We here investigated the role of scavenger receptor class B type I (SR-BI) and CD36 in mediating inhibitory effects of native HDL3 on thrombin-induced platelet activation. Methods and resultsRhodamine isothiocyanate-labeled HDL3 bound specifically to platelets and HDL3 binding was inhibited by scavenger receptor class B ligands such as phosphatidylserine (PS)- or phosphatidylinositol (PI)-containing liposomes or maleylated albumin (mBSA). By contrast, scavenger receptor class A ligands failed to displace HDL3 from platelets. HDL3, PS- and PI-liposomes, and mBSA inhibited thrombin-induced platelet aggregation, fibrinogen binding, P-selectin expression and mobilization of intracellular Ca2+. In addition, PS- and PI-liposomes emulated HDL3-induced intracellular signaling cascades including diacylglycerol production and protein kinase C activation. The reduction of platelet activation by liposomes was related to their PS or PI content. Moreover, inhibitory effects of native HDL3 were enhanced after enriching lipoproteins with PS, while PS- and PI-poor HDL2 failed to inhibit platelet aggregation and Ca2+ mobilization. Both, HDL3 and PS-containing liposomes failed to inhibit thrombin-induced activation of platelets obtained from SR-BI-deficient mice but not CD36-deficient mice. ConclusionWe suggest that SR-BI is a functional receptor for native HDL3 on platelets that generates an inhibitory signal for platelet activation. The content of negatively charged phospholipids (PS, PI) in HDL may be an important determinant of their anti-thrombotic potential.

Metabolic pathways for the degradation of phosphatidic acid in isolated nuclei from cerebellar cells

The aim of the present research was to analyse the pathways for phosphatidic acid metabolism in purified nuclei from cerebellar cells. Lipid phosphate phosphatase and diacylglyceride lipase activities were detected in nuclei from cerebellar cells. It was observed that DAGL activity makes up 50% of LPP activity and that PtdOH can also be metabolised to lysophosphatidic acid. With a nuclear protein content of approximately 40μg, the production of diacylglycerol and monoacylglycerol was linear for 30min and 5min, respectively, whereas it increased with PtdOH concentrations of up to 250μM. LysoPtdOH, sphingosine 1-phosphate and ceramide 1-phosphate, which are alternative substrates for LPP, significantly reduced DAG production from PA. DAG and MAG production increased in the presence of Triton X-100 (1mM) whereas no modifications were observed in the presence of ionic detergent sodium deoxycholate. Ca2+ and Mg2+ stimulated MAG production without affecting DAG formation whereas fluoride and vanadate inhibited the generation of both products. Specific PtdOH-phospholipase A1 and PtdOH-phospholipase A2 were also detected in nuclei. Our findings constitute the first reported evidence of active PtdOH metabolism involving LPP, DAGL and PtdOH-selective PLA activities in purified nuclei prepared from cerebellar cells.

DGKι regulates presynaptic release during mGluR-dependent LTD

Diacylglycerol (DAG) is an important lipid second messenger. DAG signalling is terminated by conversion of DAG to phosphatidic acid (PA) by diacylglycerol kinases (DGKs). The neuronal synapse is a major site of DAG production and action; however, how DGKs are targeted to subcellular sites of DAG generation is largely unknown. We report here that postsynaptic density (PSD)-95 family proteins interact with and promote synaptic localization of DGKι. In addition, we establish that DGKι acts presynaptically, a function that contrasts with the known postsynaptic function of DGKζ, a close relative of DGKι. Deficiency of DGKι in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGKι-/- synapses show a reduction in metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) at neonatal (∼2 weeks) stages that involve suppression of a decrease in presynaptic release probability. Inhibition of protein kinase C normalizes presynaptic release probability and mGluR-LTD at DGKι-/- synapses. These results suggest that DGKι requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD.

Kinetic modeling of lipase-catalyzed glycerolysis of olive oil

This work reports experimental data and the kinetic modeling of monoacylglycerols (MAG) and diacylglycerols (DAG) production from olive oil using a commercial immobilized lipase (Novozym 435) and tert-butanol as solvent. The kinetic modeling presented is based on the ordered-sequential Bi Bi mechanism considering glycerolysis and hydrolysis/esterification steps. Moreover, an empirical enzyme deactivation term, due to an excess of glycerol in the system, is proposed. The experiments were performed in batch mode evaluating the effects of temperature (40–70 °C), enzyme concentration (2.5–15 wt%) and glycerol to oil (G:O) molar ratio (0.5:1.5–6:1). Good conversions of MAG (∼65 wt%) and DAG (∼57 wt%) were obtained with relatively low enzyme concentrations (10 wt %) in relatively short reaction times (720 min) for different initial G:O molar ratios. A very satisfactory agreement between the experimental data and modeling results was obtained under various conditions of enzyme concentration, glycerol to olive oil molar ratio and temperature, thus allowing a better understanding of the reaction kinetics.

Regulation of hippocampal long‐term potentiation and long‐term depression by diacylglycerol kinaseζ

Diacylglycerol (DAG) is an important signaling molecule at neuronal synapses. Generation of synaptic DAG is triggered by the activation of diverse surface receptors including N-methyl-D-aspartate (NMDA) receptors and metabotropic glutamate receptors. The action of DAG is terminated by enzymatic conversion of DAG to phosphatidic acid (PA) by DAG kinases (DGKs). DGKζ, one of many mammalian DGKs, is localized to synapses through direct interaction with the postsynaptic scaffolding protein PSD-95, and regulates dendritic spine maintenance by promoting DAG-to-PA conversion. However, a role for DGKζ in the regulation of synaptic plasticity has not been explored. We report here that Schaffer collateral-CA1 pyramidal synapses in the hippocampus of DGKζ-knockout (DGKζ(-/-) ) mice show enhanced long-term potentiation (LTP) and attenuated long-term depression (LTD). The attenuated LTD at DGKζ(-/-) synapses involves both NMDA receptors and metabotropic glutamate receptors. These changes in LTP and LTD were reversed by phospholipase C inhibition, which blocks DAG production. Similar reversals in both LTP and LTD were also induced by inhibition of protein kinase C, which acts downstream of DAG. These results suggest that DGKζ regulates hippocampal LTP and LTD by promoting DAG-to-PA conversion, and establish that phospholipase C and protein kinase C lie upstream and downstream, respectively, of DGKζ-dependent regulation of hippocampal LTP and LTD.

Production of diacylglycerols from glycerol monooleate and ethyl oleate through free and immobilized lipase-catalyzed consecutive reactions

The ability of free and immobilized lipase on the production of diacylglycerols (DAG) by transesterification of glycerol monooleate (GMO) and ethyl oleate was investigated. Among three free lipases such as lipase G (Penicillium cyclopium), lipase AK (Pseudomonas fluorescens) and lipase PS (Pseudomonas cepacia), lipase PS exhibited the highest DAG productivity, and the DAG content gradually increased up to 24 hours reaction and then remained steady. The comparative result for DAG productivity between free lipase PS and immobilized lipases (lipase PS-D and Lipozyme RM IM) during nine times of 24 hours reaction indicated that total DAG production was higher in immobilized lipase PS-D (183.5mM) and Lipozyme RM IM (309.5mM) than free lipase PS (122.0mM) at the first reaction, and that the DAG production rate was reduced by consecutive reactions, in which more sn-1,3-DAG was synthesized than sn-1,2-DAG. During the consecutive reactions, the activity of lipase PS was relatively steady by showing similar DAG content, whereas DAG production of lipase PS-D and Lipozyme RM IM was gradually decreased to 69.9 and 167.1mM at 9th reaction, respectively, resulting in 62% and 46% reduced production when compared with 1st reaction. Interestingly, from 7th reaction lipase PS produced more DAG than immobilized lipase PS-D, and exhibited a stable activity for DAG production. Therefore, the present study suggested that DAG productivity between GMO and ethyl oleate was higher in immobilized lipases than free lipases, but the activity was reduced with repeated uses.

A phosphorylation-regulated amphipathic helix controls the membrane translocation and function of the yeast phosphatidate phosphatase

Regulation of membrane lipid composition is crucial for many aspects of cell growth and development. Lipins, a novel family of phosphatidate (PA) phosphatases that generate diacylglycerol (DAG) from PA, are emerging as essential regulators of fat metabolism, adipogenesis, and organelle biogenesis. The mechanisms that govern lipin translocation onto membranes are largely unknown. Here we show that recruitment of the yeast lipin (Pah1p) is regulated by PA levels onto the nuclear/endoplasmic reticulum (ER) membrane. Recruitment requires the transmembrane protein phosphatase complex Nem1p-Spo7p. Once dephosphorylated, Pah1p can bind to the nuclear/ER membrane independently of Nem1p-Spo7p via a short amino-terminal amphipathic helix. Dephosphorylation enhances the activity of Pah1p, both in vitro and in vivo, but only in the presence of a functional helix. The helix is required for both phospholipid and triacylglycerol biosynthesis. Our data suggest that dephosphorylation of Pah1p by the Nem1p-Spo7p complex enables the amphipathic helix to anchor Pah1p onto the nuclear/ER membrane allowing the production of DAG for lipid biosynthesis.

Spatial Regulation of Membrane Fusion Controlled by Modification of Phosphoinositides

Membrane fusion plays a central role in many cell processes from vesicular transport to nuclear envelope reconstitution at mitosis but the mechanisms that underlie fusion of natural membranes are not well understood. Studies with synthetic membranes and theoretical considerations indicate that accumulation of lipids characterised by negative curvature such as diacylglycerol (DAG) facilitate fusion. However, the specific role of lipids in membrane fusion of natural membranes is not well established. Nuclear envelope (NE) assembly was used as a model for membrane fusion. A natural membrane population highly enriched in the enzyme and substrate needed to produce DAG has been isolated and is required for fusions leading to nuclear envelope formation, although it contributes only a small amount of the membrane eventually incorporated into the NE. It was postulated to initiate and regulate membrane fusion. Here we use a multidisciplinary approach including subcellular membrane purification, fluorescence spectroscopy and Förster resonance energy transfer (FRET)/two-photon fluorescence lifetime imaging microscopy (FLIM) to demonstrate that initiation of vesicle fusion arises from two unique sites where these vesicles bind to chromatin. Fusion is subsequently propagated to the endoplasmic reticulum-derived membranes that make up the bulk of the NE to ultimately enclose the chromatin. We show how initiation of multiple vesicle fusions can be controlled by localised production of DAG and propagated bidirectionally. Phospholipase C (PLCγ), GTP hydrolysis and (phosphatidylinsositol-(4,5)-bisphosphate (PtdIns(4,5)P2) are required for the latter process. We discuss the general implications of membrane fusion regulation and spatial control utilising such a mechanism.

Improvement of mono and diacylglycerol production via enzymatic glycerolysis in tert‐butanol system

AbstractIn this work we report experimental data regarding the glycerolysis of olive oil using Novozym 435 in tert‐butanol organic system aiming at the production of monoacylglycerols (MAG) and diacylglycerols (DAG). Experiments were performed in batch mode, recording the reaction kinetics and evaluating the effects of temperature, enzyme concentration, tert‐butanol:oil/glycerol volume ratio and using solvent to substrates ratio of 1:1 and 5:1 v/v. Experimental results showed that lipase‐catalyzed glycerolysis in tert‐butanol might be a potential route for the production of high contents of MAG and DAG. The results also showed that it is possible to maximize the production of MAG and/or DAG, depending on the glycerol to oil molar ratio employed in the reactional system. Higher contents of MAG (53 wt%) and DAG (50 wt%) were achieved using glycerol to oil molar ratio of 3:1/6:1 and 0.5:1.5, respectively, both in 8 h of reaction at 70°C, 600 rpm and enzyme concentration of 10 wt%.

A Diacylglycerol-Dependent Signaling Pathway Contributes to Regulation of Antibacterial Autophagy

Autophagy mediates the degradation of cytoplasmic contents in the lysosome and plays a significant role in immunity. Lipid second messengers have previously been implicated in the regulation of autophagy. Here, we demonstrate a signaling role for diacylglycerol (DAG) in antibacterial autophagy. DAG production was necessary for efficient autophagy of Salmonella, and its localization to bacteria-containing phagosomes preceded autophagy. The actions of phospholipase D and phosphatidic acid phosphatase were required for DAG generation and autophagy. Furthermore, the DAG-responsive delta isoform of protein kinase C was required, as were its downstream targets JNK and NADPH oxidase. Previous studies have revealed a role for the ubiquitin-binding adaptor molecules p62 and NDP52 in autophagy of S. Typhimurium. We observed bacteria-containing autophagosomes colocalizing individually with either DAG or ubiquitinated proteins, indicating that both signals can act independently to promote antibacterial autophagy. These findings reveal an important role for DAG-mediated PKC function in mammalian antibacterial autophagy.

Calcium Transduces Plasma Membrane Receptor Signals to Produce Diacylglycerol at Golgi Membranes

Protein kinase C and protein kinase D are potently activated by agonist-evoked increases in diacylglycerol. Using live cell-imaging probes for kinase activity, we have shown that both kinases are robustly activated at the Golgi following stimulation of G(q)-coupled receptor signaling pathways, displaying activation signatures at the Golgi that are distinct from those at the plasma membrane. Here we report that Ca(2+) is the mediator that allows signals received at the plasma membrane to activate these two protein kinases at the Golgi. Specifically, using fluorescence resonance energy transfer-based reporters to image diacylglycerol production, we show that Ca(2+) is necessary and sufficient to elevate diacylglycerol levels at the Golgi. First, raising intracellular Ca(2+) by treating cells with thapsigargin induces diacylglycerol production at the Golgi. Second, chelation of intracellular Ca(2+) prevents UTP-stimulated increases in diacylglycerol at the Golgi. Thus, agonist-evoked increases in intracellular Ca(2+) cause increases in Golgi diacylglycerol, allowing this intracellular membrane to serve as a platform for signaling by protein kinases C and D.

Phosphatidylinositol 4,5-bisphosphate-dependent regulation of the output in lobster olfactory receptor neurons

Transient receptor potential (TRP) channels often play a role in sensory transduction, including chemosensory transduction. TRP channels, a common downstream target of phosphoinositide (PI) signaling, can be modulated by exogenous phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] and/or diacylglycerol (DAG). Lobster olfactory receptor neurons (ORNs) express a TRP-related, non-selective, calcium/magnesium-permeable, sodium/calcium-gated cation (SGC) channel. Here we report that PIs regulate the function of the calcium-activated form of the lobster channel. Sequestering of endogenous PI(4,5)P2, either with an anti-PI(4,5)P2 antibody or by electrostatic screening with polyvalent cations, blocks the channel. Exogenous PI(3,4,5)P3 activates the channel independently of intracellular sodium and/or calcium. Exogenous non-hydrolysable DAG analogs fail to change the gating parameters of the channel, suggesting the channel is insensitive to DAG. Electrophysiological recording from lobster ORNs in situ using a panel of pharmacological tools targeting the key components of both PI and DAG metabolism (phospholipase C, phosphoinositide 4-kinase and DAG kinase) extend these findings to the intact ORN. PI(4,5)P2 depletion suppresses both the odorant-evoked discharge and whole-cell current of the cells, and does so possibly independently of DAG production. Collectively, our results argue that PIs can regulate output in lobster ORNs, at least in part through their action on the lobster SGC channel.

Diacylglycerol production at the Golgi: regulation by Ca2+

Protein kinase C and protein kinase D are potently activated by agonist‐evoked increases in diacylglycerol. Using live cell‐imaging probes for kinase activity, we have previously shown that both kinases are robustly active at the Golgi following stimulation of Gq‐coupled receptor signaling pathways, displaying activation signatures at the Golgi that are distinct from those at the plasma membrane. Here we address the mechanism by which signals received at the plasma membrane cause these two protein kinases to be activated at the Golgi. Using FRET‐based reporters to image diacylglycerol production, we show that Ca2+ is necessary and sufficient to transduce signals from the plasma membrane to the Golgi. First, chelation of intracellular Ca2+ prevents UTP‐dependent increases in diacylglycerol at the Golgi, but not plasma membrane. Second, raising intracellular Ca2+ by treating cells with thapsigargin induces diacylglycerol production at the Golgi. Thus, agonist‐evoked increases in intracellular Ca2+ cause increases in Golgi diacylglycerol, allowing this intracellular membrane to serve as a platform for signaling by protein kinases C and D.This work was supported by NIH GM43154 and NIH DK54441.

Production of diacylglycerols through low-temperature chemical glycerolysis

The aim of this study was to produce diacylglycerols (DAG) by chemical glycerolysis of soybean oil at low temperatures. Solvents and low-frequency ultrasonic irradiation were introduced to enhance the reaction. Three operation modes, namely mechanical stirring, magnetic stirring and ultrasonic irradiation, were compared. In the solvent-free system, DAG formation was not observed in any of the three operation systems. DAG were formed when reactions were incubated in tertiary alcohols for all of the three operation systems. Interesting observations were found in the acetone system. Although DAG formation was negligible under mechanical stirring with classical propeller, a total of 52.0 ± 2.2% DAG was obtained when ultrasonic irradiation was used. The same content of DAG can also be obtained under magnetic stirring; however, a 4-h reaction was required. Acetone dosage (solvent:oil, wt:wt) 3:1 and 40 W ultrasonic power were suitable for the reaction system under the conditions studied.

Polyunsaturated fatty acids in the modulation of T-cell signalling

n-3 Polyunsaturated fatty acids (PUFA) have been shown to modulate immune responses. These agents, being considered as adjuvant immunosuppressants, have been used in the treatment of various inflammatory and autoimmune diseases. However, the molecular mechanisms of action of n-3 PUFA-induced immunosuppressive effects are not well-understood. Since exogenous n-3 PUFA, under in vitro and in vivo conditions, are efficiently incorporated into T-cell plasma membranes, a number of recent studies have demonstrated that these agents may modulate T-cell signalling. In this review, the interactions of n-3 PUFA with the second messenger cascade initiated during early and late events of T-cell activation are discussed. We particularly focus on how these fatty acids can modulate the production of diacylglycerol and the activation of protein kinase C, mitogen activated protein kinase, calcium signalling and translocation of transcriptional factors, implicated in the regulation of gene transcription in T-cells.