Nuclear diacylglycerol is increased during cell proliferation <i>in vivo</i>

Banfíƈ, Hrvoje; Žižak, Mirza; Divecha, Nullin; Irvine, Robin F.

doi:10.1042/bj2900633

Cited by 115 publications

(86 citation statements)

References 24 publications

(36 reference statements)

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“…5). Increased production of nuclear DG upon cell stimulation has been detected in many cells [30,31], and the importance of the nuclear localization of protein kinases C has been addressed [32]. It is thus likely that DGKc~ is the isozyme participating in the metabolic processing of nuclear DG.…”

Section: Resultsmentioning

confidence: 99%

Translocation of diacylglycerol kinase α to the nuclear matrix of rat thymocytes and peripheral T‐lymphocytes

et al. 1996

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The cytosolic ~-diacylglycerol kinase (DGK) was translocated to and tightly associated with the nuclear matrix when rat thymocytes and peripheral T-lymphocytes were stimulated with concanavalin A or anti-T-cell receptor antibody. This translocation occurred rather slowly and was completed in 3-4 h after cell stimulation. We also detected significant accumulation of nuclear phosphatidic acid interpreted as being formed by the translocated enzyme. The enzyme translocation is not directly linked to pbospboinositide turnover and protein pbospborylation, since pborbol myristate acetate and calcium ionopbore did not affect the cellular DGK(x and since we detected no covalent modification of the enzyme molecule. Although the mechanisms underlying the enzyme translocation remain unknown, our results indicate that DGKcx participates in nuclear pbospbollpid metabolism occurring at the intermediate stage of lymphocyte activation.Key words." Diacylglycerol kinase, c~-isozyme; T-lymphocyte, rat; Translocation; Nuclear matrix elucidated by the finding that DGKa could account for the most of the DGK activity, which was rapidly increased after IL-2 stimulation of T-cell lines [18]. However, the role of DGKc~ in phosphoinositide turnover and in other biochemical events preceding the expression of IL-2 receptors remains unknown. For example, exogenous short-chain DG repeatedly administered to human T-lymphocytes was phosphorylated by cellular DGK only to a negligible extent [19]. Van der Bend et al. [20] proposed a topological sequestration of cellular DGK molecules based on the finding that DG artificially generated by treating Jurkat and other cells with bacterial phospholipase C could not serve as substrate for the cellular DGK. These observations indicate that the metabolic role of DGKa abundantly contained in T-lymphocytes is still largely unknown and that the cellular DGKs are operating under strict control mechanisms. Here we describe a targeting of DGKc~ to the nuclear matrix upon T-cell activation and suggest the participation of this DGK isozyme in the nuclear phospholipid metabolism occurring in stimulated lymphocytes.

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Section: Resultsmentioning

confidence: 99%

Translocation of diacylglycerol kinase α to the nuclear matrix of rat thymocytes and peripheral T‐lymphocytes

et al. 1996

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“…Most of the data collected to date by ourselves and others [5][6][7]9] have utilized nuclei that have been stripped of their envelopes by detergents. Moreover, we have so far assumed that nuclear inositides are the major source of the DAG generated in this location, which in turn probably serves to recruit protein kinase C to the nucleus [5] and activate it.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the relative contribution of the nuclear envelope to nuclear inositide metabolism remains to be elucidated. Most studies of inositol lipids involving nuclei have required removal of the nuclear envelope before lipid analysis [5][6][7]. However, when Jarpe et al [8] investigated the source of DAG generated from isolated, entirely intact nuclei, they concluded that phosphatidylcholine, rather than inositides, was the primary source.…”

Section: Introductionmentioning

confidence: 99%

Metabolism and possible compartmentalization of inositol lipids in isolated rat-liver nuclei

Vann

Wooding

Irvine

et al. 1997

Biochemical Journal

116

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(1) The removal of the nuclear envelope from isolated rat-liver nuclei by washing with Triton X-100 (TX-100) was assessed by electron microscopy. All the envelope was removed by 0.04 % (w\v) TX-100. (2) After this removal, phosphorylation of inositol lipids and diacylglycerol (DAG) from [γ-$#P]ATP still occurs, despite the near complete absence of detectable (by mass assay) DAG and PtdIns. This suggests that the majority of these two lipids in nuclei are present in the nuclear membrane, but the small amounts remaining after extraction, defined as intranuclear, are available for phosphorylation by lipid kinases (36 % for DAG and 24 % for PtdIns respectively, when expressed as a percentage of incorporation of intact nuclei). (3) PtdIns(4,5)P # did not follow the same pattern as PtdIns and DAG ; after removal of the nuclear membrane, 40 % of the mass of this lipid was left in the nucleus. Moreover, a similar amount of PtdIns(4,5)P # was also resistant to extraction with even higher concentrations of detergent, suggesting that PtdIns(4,5)P # has a discrete intranuclear location, probably bound to nuclear proteins. (4) Addition of exogenous substrates, PtdIns, PtdIns(4)P and DAG, to membrane-depleted nuclei resulted in reconstitution of the majority of lipid phosphorylations from [γ-$#P]ATP (70 %, 90% and 94 % of intact nuclei respectively),

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“…Nuclear phospholipase C-β 1 IGF-mediated PtdIns(4,5)P 2 hydrolysis and DAG generation in membrane-depleted nuclei of Swiss 3T3 cells pointed to the possible involvement of phospholipase C (20), and the activation of the nuclear PI-PLC-β 1 in response to IGF-I was later confirmed (46,47). In vivo model of regenerating rat liver showed the similar increase in the level of the nuclear DAG 20 hours after partial hepatectomy (5). The early immunoanalysis of isolated rat liver nuclei for the presence of various PI-PLC isoforms demonstrated the nuclear presence of PI-PLC-β 1 (21).…”

Section: Nuclear Phospholipase Cmentioning

confidence: 76%

“…In addition to providing the survival signal in PC12 cells, the nuclear PI3K class I activation and PtdIns (3,4,5 …”

Section: Nuclear Pi 3-kinase In Myeloid Differentiationmentioning

confidence: 99%

Nuclear phospholipid signaling: phosphatidylinositol-specific phospholipase C and phosphoinositide 3-kinase

Višnjić

Banfíƈ

2007

Pflugers Arch - Eur J Physiol

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Over the last 20 years, numerous studies have demonstrated the existence of nuclear phosphoinositide signaling distinct from the one at the plasma membrane. The activation of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphoinositide 3-kinase (PI3K), the generation of diacylglycerol (DAG) and the accumulation of the 3-phosphorylated phosphoinositides have been documented in the nuclei of different cell types.In this review, we summarize some recent studies of the subnuclear localization, mechanisms of activation and the possible physiological roles of the nuclear PI-PLC and PI-3 kinases in the regulation of cell cycle, survival and differentiation.

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Nuclear diacylglycerol is increased during cell proliferation in vivo

Cited by 115 publications

References 24 publications

Translocation of diacylglycerol kinase α to the nuclear matrix of rat thymocytes and peripheral T‐lymphocytes

Translocation of diacylglycerol kinase α to the nuclear matrix of rat thymocytes and peripheral T‐lymphocytes

Metabolism and possible compartmentalization of inositol lipids in isolated rat-liver nuclei

Nuclear phospholipid signaling: phosphatidylinositol-specific phospholipase C and phosphoinositide 3-kinase

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