UNIPROT:P51532 - FACTA Search

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Query: UNIPROT:P51532 (transcriptional activator)
6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Widespread localization, responsiveness to numerous signal transduction systems, and broad substrate specificity enable the multifunctional CaM kinase to mediate regulation of many cellular functions. The abundance and diversity of CaM kinase substrates attest to its role as a multifunctional kinase. However, expanded identification of its in situ substrates as well as the consequences of their regulation by phosphorylation needs to be accomplished. Recently identified substrates have contributed to the list of potential functions for the CaM kinase. CREB is a hormonally stimulated transcriptional activator, and CaM kinase may lie on the pathway to its activation. This pathway could provide an interface between the potentiation of Ca2+ signals by CaM kinase and longer-term modifications of neuronal gene expression. The ryanodine receptor, as well as phospholamban, are involved in cardiac Ca2+ homeostasis, and their regulation by CaM kinase phosphorylation suggests the possibility of some feedback control of intracellular Ca2+ levels by CaM kinase. Regulation of neuronal plasticity by phosphorylation of synapsin I and of postsynaptic substrates necessary for long-term potentiation is another dynamic area of investigation. The study of substrates and their functions promises to continue providing exciting insights into the control of cellular signalling by Ca2+. Molecular cloning has enabled structural comparison of neuronal isoforms of the kinase, and has revealed the existence of closely related subunits. Subunits identified to data differ substantially only in two small variable domains, yet their expression in various tissues and during the course of development is precisely controlled. What unique properties do these small variable domains impart to the different isoforms? What directs high concentrations of kinase to a particular subcellular localization, and especially to the PSD? Further molecular cloning will undoubtedly determine whether other multifunctional CaM kinases with unique structures and properties exist. Finally, studies on the autoregulatory properties of CaM kinase have provided a fascinating picture of how this molecule can alone encode responses to Ca2+ signals, potentiating both the duration and magnitude of its activity. Autophosphorylation of the Thr286 autonomy site both traps calmodulin and permits Ca(2+)-independent activity after calmodulin dissociates. Further analysis of the role of the holoenzyme structure in these modulations will help clarify remaining mechanistic questions. Studies performed during the past few years have clearly established that this Ca(2+)-independent activity is generated in situ in response to a variety of cell stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuronal Ca2+/calmodulin-dependent protein kinases. 132 38

In the activation of eukaryotic heat shock genes, the acquisition of a binding ability to specific DNA sequence by a transcriptional activator, heat shock factor (HSF), is believed to be a crucial step. The induction of this new DNA binding activity of HSF is also obtained in a cell-free system (in vitro activation) by hyperthermia or at physiological temperature by calcium ions, low pH, urea, or non-ionic detergent. We report here the in vitro activation of HSF by treating at 0 degrees C a HeLa cell-free system with the aldehyde 4-hydroxynonenal (HNE), a highly cytotoxic product of lipid peroxidation. The in vitro activation of HSF by HNE occurred only if some components of the cell-free system were not sedimented at 100,000 x g. The reason for this is unclear but the release of active HSF from nuclei of unshocked cells and the involvement of Ca2+ contained in the mitochondria and ER have been excluded. Although HNE is known to be a sulfhydryl blocking agent, the results obtained with N-ethylmaleimide suggest that different mechanisms might be involved in the in vitro activation of HSF by HNE.
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PMID:In vitro activation of heat shock transcription factor by 4-hydroxynonenal. 139 24

Upon incubation at 37 degrees C in the absence of Ca2+ ions, pathogenic yersiniae release high amounts of pYV plasmid-encoded proteins called Yops, involved in pathogenesis. Yersinia enterocolitica also express two outer membrane proteins, an adhesin called YadA and a lipoprotein called YlpA. The production of the Yops is co-ordinately regulated by a 20 kb region of the plasmid referred to as the 'Ca2+ dependence region' and containing at least four loci called virA, virB, virC, and virF. The 8.5 kb virC region, involved in the specific transport of the Yops, is a single operon containing 13 open reading frames called yscA to yscM. Gene virF encodes a key transcriptional activator of the yop, yadA and ylpA genes. It is only transcribed at 37 degrees C and its expression is modulated by a chromosome-encoded histone-like protein called YmoA. We show here that virF also controls the virC operon. By contrast, virF is not essential for the induction of virA and virB. The VirF protein binds specifically to yop promoters. In particular, it protects the region spanning nucleotides -64 to -34 of yopH. In order to analyse the role of temperature in the induction of the yop regulon, we constructed Y. enterocolitica strains expressing virF from the tac promoter. In spite of the fact that virF was transcribed at 25 degrees C, neither the Yops nor YadA were expressed at that temperature. This poor response to VirF at 25 degrees C was at least partially due to a weak and slow transcription of the genes controlled by virF. Surprisingly, when cloned on pACYC184, gene yadA was expressed even in absence of VirF, but remained thermodependent. Hence temperature and virF are both required for the induction of the yop regulon. Among other possible roles, temperature could modify the structure of either the activator itself or the yop promoter. The fact that VirF binds in vitro to yop promoters at 25 degrees C rules out the first hypothesis. In order to test the second hypothesis, we studied, in vivo, the activity of the yopH promoter in ymoA mutants. The yopH promoter became active in the absence of VirF, indicating that yop promoter activity depends upon chromatin structure. We conclude from these two observations that, in vivo, temperature is required to modify the DNA structure of the yop promoters in order to allow the action of the transcriptional activator.
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PMID:Role of the transcriptional activator, VirF, and temperature in the expression of the pYV plasmid genes of Yersinia enterocolitica. 155 53

The Tar-EnvZ hybrid molecule (Taz1) is an inner membrane transducer that activates OmpR, a transcriptional activator for porin gene expression (ompC), in response to an aspartic acid signal. Signal transduction by Taz1 most likely involves a phosphorylated Taz1 intermediate that donates its phosphate to OmpR. Phosphorylated OmpR has already been implicated in transcriptional activation of porin genes. Using a cell-free system containing Taz1-enriched membrane fractions, we have examined the phosphorylation properties of Taz1 and the stimulatory effects of divalent and monovalent ions. Highest activation of Taz1 phosphorylation was observed with CaCl2, and its stimulation could be observed with as low as 60 microM of CaCl2. Phosphorylated Taz1 could readily donate its phosphate group to OmpR in the presence of calcium. CaCl2 was also able to enhance phosphorylation of intact membrane-bound EnvZ and a cytoplasmic fragment of EnvZ lacking the receptor and transmembrane domains. These results indicate that the site for CaCl2 stimulation is within the cytoplasmic region of EnvZ and probably involves an enhanced rate of EnvZ phosphorylation.
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PMID:Ca2(+)-enhanced phosphorylation of a chimeric protein kinase involved with bacterial signal transduction. 185 Apr 14

Upon incubation at 37 degrees C in the absence of Ca2+ ions, pathogenic yersiniae release large amounts of pYV plasmid-encoded proteins called Yops that are involved in pathogenesis. Yersinia enterocolitica also expresses an outer membrane protein that is considered an adhesin and called YadA (previously called P1 or YopA). The production of Yops is coordinately regulated by a 20-kb region of the plasmid referred to as the Ca2+ dependence region and containing at least four loci called virA, virB, virC, and virF. The virF gene encodes a key transcriptional activator of yop genes. We have shown here that virF is also required for transcription of yadA and that virB is necessary for full transcription of the yop and yadA genes. In contrast, mutations in genes virA and virC had only a weak influence on the transcription of yop and yadA genes. These mutations did not affect the production of YadA but they completely inhibited the translocation of Yops from the intracellular compartment to the extracellular milieu. We inferred from these data that virA and virC are involved in the specific transport of Yops. We analyzed the 8.5-kb virC region and showed that it is most probably a single operon containing 13 open reading frames called yscA to yscM (for Yop secretion). Protein YscC has a putative signal sequence and shares significant homology with outer membrane proteins involved in the secretion of pullulanase by Klebsiella pneumoniae (PulD) or in the assembly of filamentous bacteriophages (gene IV product). At least the putative products of yscD, yscJ, and yscL were shown to be required for the export of Yops. YscJ turned out to be YlpB, a lipoprotein that we had detected previously. The yscM gene shares homology with yopH, the adjacent gene on the pYV plasmid. Its product does not appear to be necessary for the production of Yops. Transcription of the virC operon was subjected to the same regulation as the yop genes.
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PMID:Analysis of virC, an operon involved in the secretion of Yop proteins by Yersinia enterocolitica. 186 Aug 16

Virulent yersiniae (Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica) restrict their growth at 37 degrees C in rich medium deprived of calcium. This property, called calcium dependency, correlates with the secretion of Yersinia outer membrane proteins (Yops) and with pathogenicity. It is mediated by a 70-kilobase plasmid called pYV. The structural genes of the Yops (yop genes), as well as genes involved in the control of their expression (vir genes), have been localized on pYV. In this communication we show that virF encodes a transcriptional activator controlling the yop regulon. This activator is a 30,879-dalton protein related to AraC, the regulator of the Escherichia coli and Salmonella typhimurium arabinose operons. We also show in this paper that transcription of virF is thermodependent and presumably autoregulated. virF is thus responsible for the effect of temperature on the production of the Yops. Finally, we show that virF activates transcription of the yop genes independently of the presence of calcium ions. The role of calcium therefore remains unaccounted for.
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PMID:Homology between virF, the transcriptional activator of the Yersinia virulence regulon, and AraC, the Escherichia coli arabinose operon regulator. 264 92

Gastrin gene expression was observed in two permanent rat insulinoma (RIN) cell lines derived from a rat insulinoma. Gastrin expression was selective; highest expression was seen in a cell line which did not express other islet cell hormones. Gastrin mRNA transcription initiated from the same promoter as antral gastrin mRNA. DNA transfection studies with a gastrin chloramphenicol acetyltransferase chimeric gene showed higher expression in gastrin-expressing RIN cells than non-gastrin-expressing islet cells. This implies that gastrin-expressing RIN cells selectively express a trans-acting transcriptional activator which binds to cis-acting regulatory sequences within the 5'-flanking DNA sequence and first exon of the gastrin gene. The gastrin peptide precursor synthesized in these RIN cell lines is subject to the same repertoire of posttranslational modifications within the cell's secretory apparatus (endoproteolytic cleavage, tyrosine sulfation, and C-terminal amidation) as seen in antral G cells. Gastrin mRNA levels in these RIN cells were selectively increased by increasing the extracellular calcium concentration. Membrane depolarization also stimulated gastrin mRNA levels, probably through activation of voltage-sensitive calcium channels. Thus, these gastrin-expressing RIN cell lines provide permanent cell lines useful in analyzing the cellular regulation of gastrin gene expression.
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PMID:Gastrin gene expression and regulation in rat islet cell lines. 305 95

Nuclear factor of activated T-cells (NFAT) is a transcriptional activator that binds to the interleukin-2 promoter and is believed to be responsible for T-cell-specific interleukin-2 gene expression. Here we demonstrate using electrophoretic mobility shift assays that nuclear NFAT can be induced in the rat basophilic leukemia (RBL-2H3) mast cell line and rat bone marrow-derived mast cells upon cross-linkage of the high affinity receptor (Fc epsilon RI) for immunoglobulin E (IgE). Receptor-dependent activation of NFAT was mimicked by the combination of the protein kinase C activator phorbol myristate acetate and the calcium ionophore ionomycin. The induced binding activity was specific for the NFAT recognition motif because competition with nonradioactive NFAT oligonucleotide abolished the DNA binding activity, whereas nonradioactive oligonucleotides recognized by the transcription factors NF kappa B, glucocorticoid receptors, and TFIID did not. An oligonucleotide representing the AP-1 recognition sequence also blocked the NFAT DNA binding activity, as did a combination of anti-Fos and anti-Jun antibodies. Using electrophoretic mobility shift assays, AP-1-binding proteins were found to be induced in RBL-2H3 cells under the same conditions as was the NFAT binding activity. Together these data suggest that the NFAT complex in mast cells contains Fos and Jun proteins as does NFAT in T-cells. The appearance of nuclear NFAT binding activity was dependent in part upon calcium mobilization, as buffering the antigen-induced calcium rise with intracellular BAPTA strongly inhibited NFAT activation. Prevention of calcium influx with external EGTA also inhibited NFAT activation, indicating that release of calcium from internal stores was insufficient for sustained activation of mast cell NFAT. Cyclosporin A, a potent inhibitor of the calmodulin-dependent phosphatase calcineurin, blocked the induction of NFAT-DNA binding activity, implicating calcineurin as a key signaling enzyme in this pathway. These results suggest that NFAT is present in the mast cell line RBL-2H3 and in primary bone marrow-derived mast cells, is similar in subunit composition to the T-cell NFAT, and may play a role in calcium-dependent signal transduction in mast cells.
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PMID:Fc epsilon RI-mediated induction of nuclear factor of activated T-cells. 760 2

The plant hormone abscisic acid (ABA) regulates the development and germination of seeds, as well as the adaptation of vegetative tissues to conditions of environmental stress. During the past year, considerable insights have been gained into the molecular nature of the complex signaling network that mediates the actions of ABA. Biophysical studies indicate that at least some of the effects of ABA in stomatal guard cells involve intracellular receptors. Also, increasing evidence supports the view that guard cells contain redundant ABA transduction pathways, and that cytoplasmic Ca2+ acts as a second messenger in at least one of these pathways. Finally, mutational analysis in Arabidopsis indicates that the multiple effects of ABA at the whole plant level are mediated by overlapping branches of a highly ramified signaling network. Two Arabidopsis loci that determine ABA sensitivity have already been cloned and found to encode a protein phosphatase and a transcriptional activator.
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PMID:Abscisic acid signaling. 761 76

Pathogenic yersiniae require Ca2+ for growth at 37 degrees C. They harbor closely related plasmids of about 70 kb that are essential for virulence. At 37 degrees C and in the absence of Ca2+ ions, these plasmids cause a decrease in growth rate and the release of large amounts of proteins called Yops. Here we describe the virG gene of Yersinia enterocolitica; virG is located just upstream of the virF gene, which encodes the transcriptional activator of some plasmid virulence factors. Analysis of the VirG amino acid sequence suggested that virG encodes a lipoprotein, which was confirmed by [3H]palmitate labeling of VirG-PhoA fusion proteins. A nonpolar virG mutant was constructed and found to be Ca2+ independent for growth at 37 degrees C but to still secrete Yops. This phenotype was complemented by the introduction of a plasmid harboring an intact virG gene. VirG was found to be homologous to ExsB, a protein encoded by a Pseudomonas aeruginosa gene located in the locus controlling exoenzyme S synthesis. Interestingly, the exsA gene, located just downstream of exsB, is also homologous to virF.
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PMID:VirG, a Yersinia enterocolitica lipoprotein involved in Ca2+ dependency, is related to exsB of Pseudomonas aeruginosa. 763 10

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