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:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electron microscopy studies demonstrate unequivocally that the observed oligonucleosome-sized secondary DNA fragmentation in human promyelocytic HL-60 cells treated with the topoisomerase inhibitors camptothecin and teniposide is correlated with the morphological changes in cell structure typical of programmed cell death (apoptosis). Since apoptosis has been associated with potential involvement of intracellular signaling linked to the Ca2+/calmodulin and protein kinase C transduction pathways, we also investigated the effects of signaling modulators on camptothecin- and teniposide-induced secondary DNA fragmentation in HL-60 cells. Neither calcium chelators, calcium/calmodulin inhibitors (calmidazolium or cyclosporine A), protein kinase C stimulation by TPA, protein phosphatase inhibition by okadaic acid, protein kinase inhibition by staurosporine, calphostin C, genistein or H7, nor cell cycle alterations by caffeine had any detectable effect. Interestingly, most of these intracellular signaling modulators were able to induce DNA fragmentation in HL-60 cells by themselves. These results may suggest that even though modulation of these signaling pathways was unable to prevent topoisomerase inhibitor-induced apoptosis, their sole deregulations could induce apoptosis in HL-60 cells. In contrast, aphidicolin blocked camptothecin-induced secondary DNA fragmentation, indicating that replication-induced DNA damage is required for camptothecin- but not teniposide-induced secondary DNA fragmentation. Zinc, 3-aminobenzamide, and spermine also modulated both camptothecin- and teniposide-induced secondary DNA fragmentation without significant alteration of topoisomerase-mediated primary DNA strand breaks. Hence, poly(ADP-ribosyl)ation and chromatin structure may be important in modulating oligonucleosome-sized DNA fragmentation associated with apoptosis in HL-60 cells treated with topoisomerase inhibitors.
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PMID:Apoptosis and its modulation in human promyelocytic HL-60 cells treated with DNA topoisomerase I and II inhibitors. 768 16

The particulate proteins of 34, 26, and 22 kDa are phosphorylated on serine residues in the rat parotid gland by activation of the cAMP-mediated signaling system. The 34 kDa protein was identified as ribosomal protein S6 by immunoprecipitation with anti S6 peptide antibody. The dephosphorylation of S6 was observed by incubation of the particulate fraction of the saponin-permeabilized cells labeled with [gamma-32P]ATP in the presence of cAMP/3-isobutyl-1-methylxanthine. The dephosphorylation of S6 was inhibited by either okadaic acid, a potent inhibitor of protein phosphatase, or Zn2+, however, neither Ca2+ nor Mg2+ showed significant effect. S6 phosphatase activities detected by using the 32P-labeled S6 peptide as a substrate were inhibited by both okadaic acid and Zn2+. These results suggest that the dephosphorylation of S6 is mediated by the okadaic acid and Zn(2+)-sensitive phosphatases in the rat parotid gland.
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PMID:Dephosphorylation of ribosomal protein S6 phosphorylated via the cAMP-mediated signaling pathway in rat parotid gland: effect of okadaic acid and Zn2+. 769 90

The catalytic subunit of the major protein phosphatase associated with bovine cardiac myofibrils was purified to homogeneity. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the enzyme revealed only one band with an apparent molecular weight of 37,000. On gel filtration chromatography, the phosphatase activity and the protein co-eluted as a single peak with an apparent molecular weight of 37,000. The purified enzyme was identified as the catalytic subunit of protein phosphatase 1, as determined by sensitivity to inhibitor 1, inhibitor 2, okadaic acid and by specific immunostaining. Evidence obtained with specific antipeptide antibodies demonstrated that this myofibril protein phosphatase was predominantly the alpha isoform of protein phosphatase 1. The purified catalytic subunit was completely inactive. It was activated by pretreatment with Co2+/trypsin in the presence of high ionic strength. Treatment with trypsin alone did not activate the latent enzyme. The enzyme was also activated by Co2+ or Mn2+ alone but not by Ca2+, Mg2+, Ni2+, Cu2+ or Zn2+. Activation of the enzyme was not reversed by removal of Co2+, but Mn(2+)-activated phosphatase activity was partially reversed when Mn2+ was removed. The catalytic subunit could form a 1:1 complex with inhibitor 2 in vitro. The resulting holoenzyme was also activated by pretreatment with Co2+. Since phosphatase 1 alpha is the major phosphatase associated with cardiac myofibril, it is suggested that it is responsible for the dephosphorylation of myosin and other myofibril phosphoproteins.
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PMID:A latent form of protein phosphatase 1 alpha associated with bovine heart myofibrils. 808 38

We report here the DNA sequence of a segment (alpha 1006.13: YBLO5) of chromosome II of Saccharomyces cerevisiae, extending over 32.5 kb. The segment contains 26 open reading frames (ORFs) from YBLO501 to YBLO526. YBL0505 corresponds to the SEC17 gene and YBL0521 to the KIP1 gene. YBL0516 contains an intron, YBL0513 shows homology with the RAT protein phosphatase and YBL0526 contains a zinc-finger motif. Disruption of 14 genes by insertion of a URA3 cassette has been performed and these mutants were analysed for their mating and sporulation ability, and for their growth on different carbon sources. YBL0515 and YBL0526 ORFs seem to be involved in the sporulation process.
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PMID:Sequencing and functional analysis of a 32,560 bp segment on the left arm of yeast chromosome II. Identification of 26 open reading frames, including the KIP1 and SEC17 genes. 815 87

We have examined the negative regulation of the 44-kDa mitogen-activated protein kinase (MAP kinase), also known as extracellular signal-regulated protein kinase 1 (ERK1), in NIH3T3 cells transfected with an expression plasmid encoding the human insulin receptor (NHIR cells). In these cells ERK1 activation is induced by two distinct stimuli, insulin and tumor-promoting agent (TPA). While insulin was found to be more potent than TPA for ERK1 activation, both stimuli produced the same transient activation pattern with a rapid peak (reached within 5 min) followed by a fast decrease within 20 min. By performing reconstitution experiments with immunoprecipitated ERK1 and lysates from NHIR cells, we showed that extracts from untreated cells exhibit an ERK1 inhibitory activity. Interestingly, this inhibitor was found to be regulated by insulin and TPA with a profile that is the mirror image of ERK1 activity. This repressing activity was sensitive to tyrosine phosphatase inhibitors, such as sodium orthovanadate and zinc acetate, but it was not affected by serine/threonine phosphatase inhibitors, such as sodium fluoride and okadaic acid. Moreover, it was possible to observe in extracts of NHIR cells an activity dephosphorylating ERK1. The time course of this phosphatase activity was comparable to that of the ERK1 inhibition, suggesting that the repressing activity could reflect a dephosphorylating action. Interestingly, phosphatase 2A treatment of extracts from 5-min TPA-treated cells (where the ERK1 inhibitor was weak) was able to induce an increase in the ERK1 repressing activity. This suggests that serine/threonine dephosphorylation of ERK1 inhibitor leads to an increase in its activity. In summary, we have shown that NHIR cells contain a regulatable ERK1 inhibitor, which is likely to be due to tyrosine phosphatase(s). We would like to suggest that such activities are key components in the fine-tuning of the MAP kinase cascade.
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PMID:Insulin and tumor-promoting agent regulate an inhibitor of the 44-kDa mitogen-activated protein kinase/extracellular signal-regulated protein kinase 1 in fibroblasts. 828 32

We have observed that soluble extracts from the extreme acidothermophilic archaebacterium Sulfolobus solfataricus contained protein phosphatase activity that was greatly stimulated by the divalent metal ions Mn2+, Mg2+, Ni2+, or Co2+. This activity apparently arose from a single enzyme since (a) stimulation by these divalent metal ions was not additive and (b) protein phosphatase activity eluted as a single peak from both a DE52 ion-exchange column and a Sephadex G-100 gel filtration column. Its apparent molecular mass was approximately 28,000 daltons. The enzyme dephosphorylated a variety of phosphoserine-containing substrates including casein, histone H2a, phosphorylase kinase, or glycogen phosphorylase. The enzyme would not dephosphorylate either histone H1 or a number of phosphotyrosine-containing compounds. It removed only half the phosphate bound to histone H2b, which is phosphorylated at two sites by the cAMP-dependent protein kinase. Protein phosphatase activity was inhibited by EDTA, Cu2+, Zn2+, NaF, inorganic phosphate, or pyrophosphate; but was unaffected by other potential activators and inhibitors such as microcystin, okadaic acid, vanadate, polyamines, or sulfhydryl modifying reagents. This enzyme represents the first protein phosphatase to be identified in any member of the third and oldest phylogenetic kingdom in nature, the archaebacteria.
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PMID:Identification of a serine/threonine-specific protein phosphatase from the archaebacterium Sulfolobus solfataricus. 838 14

We have detected a protein phosphatase activity in soluble extracts from the halophilic archaeon Haloferax volcanii. This activity was markedly stimulated by the divalent metal ions Mn2+ and Cd2+. It dephosphorylated phosphoseryl residues in casein, mixed histones, and phosphorylase a, but not phosphotyrosyl residues in reduced, carboxyamidomethylated and maleylated lysozyme. This protein phosphatase activity was inhibited by NaF, Zn2+, vanadate, molybdate, inorganic phosphate, inorganic pyrophosphate, or p-nitrophenyl phosphate, or by treatment with diethylpyrocarbonate. Activity was unaffected by other potential inhibitors or activators such as polyamines, heparin, cyclic nucleotides, Ca2+/calmodulin, tartrate, tetramisole, okadaic acid, microcystin LR, or sulfhydryl-modifying agents. The functional similarities between this protein-serine phosphatase and that previously identified in another archaeon, the extreme acidothermophile Sulfolobus solfataricus, suggest the existence of a family of divalent metal ion-stimulated protein-serine phosphatases of extremely ancient origin in the Archaea.
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PMID:A protein-serine phosphatase from the halophilic archaeon Haloferax volcanii. 839 5

Whether the anabolic effect of insulin-like growth factor-I (IGF-I) in osteoblastic MC3T3-E1 cells is modulated by zinc, an activator of bone formation, was investigated in vitro. After subculture for 3 days, the cells were cultured for 72 h with IGF-I (10(-8) M). The peptide produced a significant increase of protein concentration, deoxyribonucleic acid (DNA) content, and cell number in the cells. These increases were markedly enhanced by the presence of zinc sulfate (10(-5) M), but not zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; 10(-5) M). Also, the cellular alkaline phosphatase activity was synergistically increased by the presence of both IGF-I and zinc sulfate. Thus, effect was not seen in the presence of both insulin (10(-8) M) and zinc sulfate (10(-5) M). The effect of zinc sulfate to enhance the IGF-I-increased alkaline phosphatase activity and protein concentration in the cells was clearly prevented by the presence of cycloheximide (10(-6) M), staurosporin (10(-8) M), or okadaic acid (10(-7) M) with an effective concentration. However, staurosporin had a partial inhibiting effect on the IGF-I or the IGF-I plus zinc-induced increases in cellular protein, although okadaic acid entirely blocked the IGF-I or the IGF-I plus zinc effect. The present study demonstrates that the anabolic effect of IGF-I in osteoblastic cells is enhanced by zinc ion. The enhancement by zinc may be mediated through the signaling pathway of protein kinase C and protein phosphatase in the cells.
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PMID:Zinc modulation of insulin-like growth factor's effect in osteoblastic MC3T3-E1 cells. 853 89

The recombinant catalytic subunit of protein phosphatase 1 is produced as an inactive enzyme which can be activated by Mn2+ (Zhang, Z., Bai, G., Deans-Zirattu, S., Browner, M. F., and Lee, E. Y. C. (1992) J. Biol. Chem. 267, 1484-1490). In this report, we have investigated the effects of divalent cations on the activity of recombinant catalytic subunit of protein phosphatase 1. Latent phosphatase 1 can be activated by Co2+ or Mn2+, whereas other metal ions tested including Fe2+, Zn2+, Mg2+, Ca2+, Cu2+, or Ni2+ were not effective or were only weakly effective in activating the enzyme. The Mn(2+)-stimulated activity was susceptible to inactivation by EDTA; however, the Co(2+)-activated phosphatase was stable after dilution and chelation of the Co2+ with excess EDTA. After stable activation of phosphatase 1 using 57Co2+, a stoichiometric amount of 57Co2+ was shown to be tightly bound to phosphatase 1. These findings demonstrate for the first time the generation of a stable metalloenzyme form of phosphatase 1. Fe2+ reversibly deactivated the Co(2+)-stimulated activity, but did not displace the bound Co2+. Interestingly, treatment of the enzyme with a combination of Fe2+ and Zn2+ (but not the individual metal ions) significantly activated phosphatase 1. These results suggest that at least two metal binding sites exist on the enzyme and that protein phosphatase 1 may be an iron/zinc metalloprotein in vivo.
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PMID:Activation of protein phosphatase 1. Formation of a metalloenzyme. 857 23

A soluble protein phosphatase from the promastigote form of the parasitic protozoan Leishmania donovani was partially purified using Sephadex G-100, DEAE-cellulose and again Sephadex G-100 columns. The partially purified enzyme showed a native molecular weight of about 42,000 in both Sephadex G-100 and sucrose density gradient centrifugation. The sedimentation constant, stokes radius and frictional ratio were found to be 3.43S, 2.8 nm and 1.20 respectively. The enzyme preferentially utilized phosphohistone as the best exogenous substrate. Mg2+ ions were essential for enzyme activity; among other metal ions Mn2+ can replace Mg2+ to a certain extent whereas Ca2+, Co2+ and Zn2+ could not substitute for Mg2+. The pH optimum of the enzyme was 6.5-7.5 and the temperature optimum 37 degrees C. The apparent Km for phosphohistone was 7.14 microM. ATP, ADP, inorganic phosphate and pyrophosphate had inhibitory effect on the enzyme activity whereas no inhibition was observed with sodium tartrate and okadaic acid. These results suggest that L. donovani promastigotes possess a protein phosphatase which has similar characteristics with the mammalian protein phosphatase 2C.
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PMID:Partial purification and characterization of a soluble protein phosphatase from Leishmania donovani promastigotes. 859 23


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