Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have demonstrated that 1,25-dihydroxyvitamin D3 (D3) can activate Raf kinase and induce Egr expression in cultured rat hepatic Ito cells (Lissoos, T. W., Beno, D. W. A., and Davis, B. H. (1993) J. Biol. Chem. 268, 25132-25138). Since Raf is an upstream activator of mitogen-activated protein kinase (MAPK), the current study evaluated the ability of D3 to activate MAPK. D3-activated MAPK and induced its cytoplasmic to perinuclear translocation in Ito cells. MAPK activation was found to be protein kinase C-dependent, which was analogous to previous studies of D3 and Raf activation. To further explore the D3 cascade, a series of transient transfections were performed using dominant negative raf and MAPK mutant plasmids which effectively block Ras-induced Raf and MAPK activity, respectively. D3 induced a marked increase in the expression of a chloramphenicol acetyltransferase reporter gene linked to the Egr promoter (egr-CAT). When the dominant negative Raf plasmid was co-transfected, there was no significant reduction in egr-CAT. In contrast, when the dominant negative MAPK plasmid was co-transfected, egr-CAT induction was completely abolished. These results suggest that 1) D3 stimulates MAPK via a protein kinase C-dependent pathway, 2) D3-induced Egr expression can occur via a pathway independent of Ras-induced Raf, and 3) D3 absolutely requires MAPK activity for Egr expression.
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PMID:Protein kinase C and mitogen-activated protein kinase are required for 1,25-dihydroxyvitamin D3-stimulated Egr induction. 787 2

The generation of dorso-ventral polarity in Drosophila relies on the formation of a nuclear gradient of the rel/nuclear factor kappa B transcription factor dorsal in the pre-cellular syncitial embryo by a process of differential nuclear localization. It is thought that the gradient is formed by activation at ventral positions of the membrane receptor Toll that in turn causes the local dissociation of dorsal from the cytoplasmic anchor protein cactus. Although Toll is related in its cytoplasmic domain to the interleukin-1 receptor little is known about the signal transduction pathways that lead from Toll to the relocalization of dorsal. In this paper we have used immunofluorescence microscopy as a direct assay of dorsal protein nuclear localization in the Drosophila cell line Schneider 2. We find that increased cytoplasmic calcium concentration and the expression of constitutively active Toll receptors can induce the relocalization of dorsal. By contrast, we find that activation of endogenous protein kinase A and expression of wild-type Toll receptors, which activate zen-chloramphenicol acetyltransferase reporter genes in this system, have only a marginal effect on the cellular distribution of the dorsal protein. Treatment of cells with activators of protein kinase C and radical oxygen intermediates, both of which activate nuclear factor kappa B, also has little effect on dorsal protein localization. We propose that different threshold levels of dorsal activation can be established by distinctly regulated signal transduction pathways.
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PMID:Relocalization of Drosophila dorsal protein can be induced by a rise in cytoplasmic calcium concentration and the expression of constitutively active but not wild-type Toll receptors. 790 39

The mechanism by which transforming Ha-ras induces c-fos expression in HC11 mouse mammary epithelial cells was investigated with regard to controversial data concerning the role of protein kinase C (PKC) and the required promoter elements of the fos gene. HC11 cells carrying a glucocorticoid-inducible Ha-ras (val12) construct were transfected with a chloramphenicol acetyltransferase (CAT) reporter gene under the control of a human fos promoter which includes the serum response element (SRE), the adjacent c-fos AP-1 site (FAP) and the cAMP response element (CRE). Induction of the Ha-ras gene by dexamethasone lead to a transactivation of expression of the transfected fos promoter construct which was inhibited by the PKC inhibitor BM41440 and abrogated in PKC-'depleted' cells. A similar transactivation was observed when the fos promoter construct was co-transfected with a constitutively active ras expression vector. Again, this effect was depressed by the PKC inhibitor and abolished in PKC-'depleted' cells. 'PKC-depletion' was achieved by long-term exposure to 12-O-tetradecanoylphorbol-13-acetate. This procedure was shown to deplete cells of PKC alpha and to reduce significantly PKC epsilon. Long-term exposure to bryostatin 1 selectively depletes PKC alpha. Depletion of PKC alpha by bryostatin 1 does not reduce the transcriptional activation of the SRE-FAP-TK-CAT (TK: thymidine kinase) construct by Ha-ras. In order to delineate the promoter elements mediating the transcriptional activation, constructs which lack the FAP and the CRE sites but contain an intact SRE were co-transfected with the ras construct. Elimination of the FAP and CRE sequences did not affect the transcriptional activation by Ha-ras (val12). It is concluded that in HC11 cells, transforming Ha-ras activates c-fos expression in a PKC-dependent manner, presumably implying PKC epsilon, and that the SRE is sufficient to mediate transcriptional activation.
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PMID:Activation of c-fos expression by transforming Ha-ras in HC11 mouse mammary epithelial cells is PKC-dependent and mediated by the serum response element. 791 86

Many hormones regulate the rate of synthesis of phosphoenolpyruvate carboxykinase (PEPCK), the enzyme that governs the rate-limiting step in gluconeogenesis. In H4IIE rat hepatoma cells, glucocorticoids, retinoic acid and cyclic AMP (cAMP) increase PEPCK gene transcription whereas insulin and phorbol esters have the opposite effect. Insulin and phorbol esters are dominant as they prevent cAMP- and glucocorticoid-stimulated PEPCK gene transcription. In contrast, insulin and phorbol esters both stimulate transcription of gene 33 in the same H4IIE cells, with the same time course as seen for their inhibitory effect on PEPCK gene transcription. We now report that the protein phosphatase inhibitor, okadaic acid, mimics the action of insulin and phorbol esters on expression of both gene 33 and PEPCK gene in H4IIE cells. Okadaic acid stimulates gene 33 mRNA accumulation whereas it inhibits cAMP- and glucocorticoid-stimulated PEPCK mRNA accumulation. The effect of okadaic acid on the PEPCK gene is mediated through the PEPCK promoter as, in a cell line, HL1C, stably transfected with a PEPCK-chloramphenicol acetyltransferase (CAT) fusion gene, okadaic acid inhibits cAMP- and glucocorticoid-stimulated CAT expression. Desensitization of the protein kinase C pathway by exposure to phorbol 12-myristate 13-acetate for 16 h abolishes the subsequent action of the phorbol ester but does not markedly affect the inhibition of cAMP- and glucocorticoid-stimulated CAT expression by insulin or okadaic acid. Even though insulin and okadaic acid appear to repress PEPCK gene expression through a pathway initially distinct from that used by phorbol esters, transient-transfection studies show that the final target of the action of okadaic acid, insulin and phorbol ester is the same DNA element.
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PMID:Comparison of the effects of insulin and okadaic acid on phosphoenolpyruvate carboxykinase gene expression. 798 Apr 40

Recent evidence demonstrates that the protein kinase C zeta (zeta PKC) isoform is required for the activation of nuclear factor kappa B (NF-kappa B) and mitogenic signaling in Xenopus oocytes and mammalian cells. The mechanism whereby zeta PKC regulates NF-kappa B most probably involves the activation of a putative I kappa B kinase of molecular mass approximately 50 kDa, which phosphorylates and inactivates I kappa B. Tumor necrosis factor alpha (TNF alpha) and interleukin-1, besides activating the phospholipase C-mediated breakdown of phosphatidylcholine, also generate ceramide, which is produced by stimulation of sphingomyelin hydrolysis. We show here that exogenous addition of sphingomyelinase (SMase) to NIH-3T3 fibroblasts transactivates a kappa B-dependent chloramphenicol acetyltransferase reporter plasmid, to an extent similar to that produced by TNF alpha or phosphatidylcholine/phospholipase C. More importantly, the ability of SMase to stimulate this parameter is severely impaired by transfection of a zeta PKC kinase-defective dominant negative mutant, which suggests a critical role of zeta PKC in SMase signaling. In keeping with this notion, we also demonstrate here that zeta PKC is activated in vitro by ceramide and in vivo by treatment of NIH-3T3 fibroblasts with SMase.
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PMID:Protein kinase C zeta isoform is critical for kappa B-dependent promoter activation by sphingomyelinase. 803 80

Ribonucleotide reductase catalyses the reaction that eventually provides the four deoxyribonucleotides required for the synthesis and repair of DNA. U.v.-cross-linking and band-shift experiments have identified in COS 7 monkey cells an approx. 57 kDa ribonucleotide reductase R1 mRNA-binding protein called R1BP, which binds specifically to a 49-nt region of the R1 mRNA 3'-untranslated region (3'UTR). The R1BP-RNA binding activity was down-regulated by the tumour promoters phorbol 12-myristate 13-acetate (PMA; 'TPA') and okadaic acid, and up-regulated by the protein kinase C inhibitor staurosporine, in a dose-dependent fashion. Furthermore, staurosporine treatment decreased the stability of R1 and CAT (chloramphenicol acetyltransferase)/R1 hybrid mRNAs, whereas PMA and okadaic acid increased the stability of these messages, in a dose-dependent manner. In contrast, treatment of cells with forskolin, a protein kinase A inhibitor, did not alter either R1BP-RNA binding or R1 mRNA-stability characteristics. Transfectants containing R1 or CAT/R1 cDNA constructs with a deletion of the 49-nt 3'UTR sequence failed to respond in message-stability studies to the effects of PMA, staurosporine or okadaic acid. These observations indicate that a protein kinase C signal pathway regulates ribonucleotide reductase R1 gene expression post-transcriptionally, through a mechanism involving a specific cis-trans interaction at a 49-nt region within the R1 mRNA 3'UTR.
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PMID:Regulation of mammalian ribonucleotide reductase R1 mRNA stability is mediated by a ribonucleotide reductase R1 mRNA 3'-untranslated region cis-trans interaction through a protein kinase C-controlled pathway. 806 98

The induction of the AP-1 transcription factor has been ascribed to the early events leading to T lymphocyte activation. We have examined the possibility that stimulation of phospholipase D (PLD) may regulate activation of transcription factor AP-1 in human T cells by transfecting human T lymphocyte Jurkat cells with a plasmid containing an AP-1 enhancer element and a chloramphenicol acetyltransferase reporter gene. We have detected activatable PLD in Jurkat cells, and we have found that addition of phosphatidic acid (PA), the physiologic product of PLD action on phospholipids, is rapidly incorporated into Jurkat cells and leads to activation of transcription factor AP-1. Treatment of Jurkat cells with anti-CD3 mAb activated both PLD and transcription factor AP-1. Wortmannin, an inhibitor of receptor-coupled PLD activation, blocked the anti-CD3-induced increases in both PLD activity and AP-1 enhancer activity. We found a good correlation in the transfected cells between PLD activation and induction of AP-1 enhancer activity under different experimental conditions. Furthermore, ethanol, an inhibitor of the PLD pathway, blocked the anti-CD3-stimulated AP-1 enhancer activity. However, this anti-CD3-mediated response was not inhibited by neomycin, an inhibitor of phosphoinositide hydrolysis. The increases in AP-1 enhancer activity induced by PA or anti-CD3 mAb were efficiently abrogated by the presence of propranolol, an inhibitor of PA phosphohydrolase and protein kinase C (PKC). Furthermore, the PA- and the anti-CD3-induced increases in AP-1 enhancer activity were blocked by the presence of PKC inhibitors or by PKC down-regulation. These data indicate that PLD stimulation can activate the transcription factor AP-1 in T lymphocytes, and suggest that the induction of AP-1 enhancer factor activity by PA is mediated via PKC stimulation, either through a direct activating effect of PA or through PA-derived diacylglycerol formation. These data also provide evidence for a role of PLD-derived lipids in the induction of AP-1 enhancer activity resulting from stimulation of the TCR/CD3 complex, suggesting that increased PLD activity can play an important role in T lymphocyte activation.
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PMID:Involvement of phospholipase D in the activation of transcription factor AP-1 in human T lymphoid Jurkat cells. 807 60

The regulation of cytosolic aspartate aminotransferase (cAspAT) gene expression by phorbol esters was investigated in the highly differentiated hepatoma cell line Fao. Phorbol 12,13-dibutyrate (PdBu) had no effect on basal activity but partially inhibited the induction of cAspAT by dexamethasone. The extent of inhibition (40%) was similar to that obtained with insulin or vanadate. The inhibitory effects of PdBu and vanadate were additive. In the case of PdBu, the inhibitory effects could be eliminated by first incubating the cells with PdBu, which down-regulates protein kinase C. In contrast, inhibition by insulin was not modified by this treatment. The molecular mechanism of PdBu action was investigated. Northern blot analysis showed that the steady-state mRNA levels of cAspAT were decreased by PdBu in the presence of dexamethasone. In addition, the transcription rate, as measured by run-on experiments, was also decreased under the same conditions. Finally, a 2.4 kb promoter fragment driving the chloramphenicol acetyltransferase gene was stably transfected into the Fao cells. The regulation of the activity of this promoter fragment by dexamethasone and PdBu was similar to the regulation of the endogenous cAspAT activity. We conclude that PdBu acts by regulating the promoter activity of the cAsPAT gene.
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PMID:Phorbol esters inhibit the glucocorticoid-mediated stimulation of cytosolic aspartate aminotransferase gene transcription. 811 Jan 86

The involvement of protein kinase C (PKC), a 12-O-tetradecanoylphorbol-13-acetate (TPA) receptor, in the transcriptional regulation of TPA-inducible genes was determined. Expression plasmids harboring full-length or kinase domain of PKC alpha and PKC delta (PKC alpha K and PKC delta K) were constructed. Transient transfection of PKC alpha K and PKC delta K into COS cells resulted in approximately 20- and 16-fold increase in phospholipid-, calcium-independent protein kinase activity. To determine the effects of overexpression of PKC alpha K and PKC delta K on the AP-1-mediated TPA-inducible genes, we transfected into COS cells the PKC alpha K or PKC delta K expression plasmids with collagenase chloramphenicol acetyltransferase (CAT) reporter construct containing one TPA responsive element (TRE), or a construct containing five synthetic TRE linked to a thymidine kinase promoter. PKC alpha K or PKC delta K overexpression resulted in a comparable increase (approximately 4-fold) in CAT activity. However, CAT activity was not increased after transfection of PKC constructs with non-TPA responsive thyroid hormone responsive elements CAT construct (delta MTV-TyRE-pCAT). We also found that deletion of the AP-1-like motif in the SV40 promoter abolished the PKC alpha K or PKC delta K-induced activity of luciferase (luc) reporter constructs. Overexpression of full-length PKC delta in COS cells also increased the activity of the CAT construct with TRE after TPA treatment. We determined the effects of overexpression of PKC alpha K and PKC delta K on transcription of the ornithine decarboxylase (ODC) gene, which has a non-AP-1 TRE. Cotransfection of PKC alpha K or PKC delta K expression plasmids with a TPA-inducible ODC luc construct (-72/+130-ODC-luc) into HeLa cells resulted in an increased luc activity. These results indicate that both PKC alpha (calcium dependent) and PKC delta (calcium independent) may mediate the transcription of TPA-inducible genes through both AP-1 and non-AP-1 sequences.
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PMID:Involvement of protein kinase C in the transcriptional regulation of 12-O-tetradecanoylphorbol-13-acetate-inducible genes modulated by AP-1 or non-AP-1 transacting factors. 814 84

Lactoferrin is present in a variety of tissues and biological fluids; however, the amount differs significantly due to differential expressions. We have previously demonstrated that the mouse lactoferrin gene is regulated by estrogen through an estrogen-response DNA element located at -349, upstream from the transcription start site (+1). In this report, we characterized by deletion and mutation analyses a cluster of mitogen-response elements located between -80 and -40 of the mouse lactoferrin promoter. We demonstrated that the chimeric chloramphenicol acetyltransferase reporter constructs (the -103 to +1 sequence of the mouse lactoferrin gene) containing the mitogen-response unit of the lactoferrin gene were stimulated by cAMP, forskolin, 12-O-tetradecanoylphorbol-13-acetate, and epidermal growth factor/recombinant transforming growth factor-alpha (EGF/TGF-alpha) in a time- and dose-dependent manner. The sequence at position -52 to -40 (mLF-CRE) of the gene conferred transcriptional activation in the presence of forskolin, cyclic AMP, and 12-O-tetradecanoylphorbol-13-acetate in transiently transfected human endometrium carcinoma RL95-2 cells, whereas the region at -80 to -60 responded to EGF/TGF-alpha stimulation. Overexpression of the catalytic unit of protein kinase C or protein kinase A in the RL95-2 cells elevated the chloramphenicol acetyl-transferase activity of the reporter construct 5-6-fold. The mobility shift assay suggested that AP1 and CREB or related proteins participated in complex formation with the mLF-CRE, whereas different proteins bound to the EGF/TGF-alpha-response element.
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PMID:Characterization of a mitogen-response unit in the mouse lactoferrin gene promoter. 817 15


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