Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that the developmentally regulated gene D2 is induced during aggregation by pulses of cAMP, which act via the cell surface receptor and consequent signal transduction pathways (W. Rowekamp and R.A. Firtel, 1980, Dev. Biol. 79, 409-418; S.K.O. Mann and R.A. Firtel, 1987, Mol. Cell. Biol. 7, 458-469; S.K.O. Mann, C. Pinko, and R.A. Firtel, 1988, Dev. Biol., in press). In this manuscript, we compare the complete derived amino acid sequence for D2 to two cloned and sequenced eukaryotic esterases and examine the requirement of the D2 gene product for development. Amino acid sequence data comparisons suggest that D2 encodes a serine esterase with strong sequence identity to Torpedo acetylcholine esterase and a Drosophila esterase. The protein has a putative leader sequence, suggesting that it is shunted into vesicles. Using an antisense gene construct driven by a Discoidin I promoter, whose transcriptional activity depends on the growth conditions of the cells, we show that inhibition of D2 mRNA accumulation results in an abnormal developmental program that includes the absence of normal streaming and incomplete aggregate formation and subsequent development. We suggest that D2 encodes an esterase function required for proper aggregation and subsequent development.
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PMID:Molecular analysis of a developmentally regulated gene required for Dictyostelium aggregation. 290 7

Vertical starch gel electrophoresis was used to resolve proteins encoded by 18 gene loci in ascaridoid nematodes. Estimates of genetic variability were made from population samples of the dog ascarid (Toxocara canis), cat ascarid (Toxocara cati), and the horse ascarid (Parascaris equorum). Levels of polymorphism and mean heterozygosity were high, which is not consistent with the hypothesis that the intestinal environment selects for monomorphism among endoparasites. Most observed allele frequencies conformed to Hardy-Weinberg equilibrium expectations as tested by chi2 goodness-of-fit, suggesting that the proteins evaluated are inherited in a Mendelian fashion and that these nematodes are mating at random. Subunit structures of the following enzymes, deduced from electrophoretic phenotypes of heterozygotes, corresponded to those of vertebrates: lactate dehydrogenase; malate dehydrogenase; 6-phosphogluconate dehydrogenase; phosphoglucomutase; esterase D; peptidase B; peptidase D; and mannose-6-phosphate isomerase. This observation substantiates the conservative nature of polypeptide subunit number across phylogenetically diverse groups of organisms.
Mol Biochem Parasitol 1986 Jan
PMID:Biochemical polymorphism in Parascaris equorum, Toxocara canis and Toxocara cati. 293 2

3,5-Dimethyl-N-acetyl-p-benzoquinone imine (3,5-dimethyl-NAPQI) was cytotoxic to isolated hepatocytes from Sprague Dawley rats at levels between 200 and 300 microM. It rapidly oxidized intracellular glutathione within 10 sec, with the formation of oxidized glutathione. The cytotoxicity of 3,5-dimethyl-NAPQI could be prevented over a 3.5-hr period with the carboxylesterase inhibitor bis(p-nitrophenyl) phosphate, indicating that cytotoxicity involved N-deacetylation. The N-deacetylated product could be trapped with glutathione as 3-(glutathion-S-yl)-4-amino-2,6-dimethylphenol in 3,5-dimethyl-NAPQI-treated hepatocytes but not in hepatocytes pretreated with bis(p-nitrophenyl) phosphate, indicating that N-deacetylation activity had been inhibited. 3,5-Dimethyl-NAPQI was readily N-deacetylated by rat liver microsomes, in contrast to 3,5-dimethylacetaminophen. The latter was also not cytotoxic to hepatocytes at up to 2 mM. The N-deacetylated product 4-amino-2,6-dimethylphenol rapidly underwent autoxidation to form 2,6-dimethylbenzoquinone imine and was highly cytotoxic to hepatocytes at 200-300 microM. The latter reacted with glutathione to give the above conjugate and no glutathione oxidation occurred. Dithioerythritol (2 mM) added at 10, 20, and 30 min after 3,5-dimethyl-NAPQI delayed but did not prevent cytotoxicity. Dithioerythritol also resulted in the partial restoration of GSH, presumably as a result of reduction of protein mixed disulphides. The mechanism of cytotoxicity of 3,5-dimethyl-NAPQI therefore appears to be a result of a combination of oxidative stress and deacetylation resulting in arylation.
Mol Pharmacol 1988 Nov
PMID:The metabolism of N-acetyl-3,5-dimethyl-p-benzoquinone imine in isolated hepatocytes involves N-deacetylation. 319 58

Both interleukin-1 alpha (IL-1 alpha) and IL-1 beta are initially translated as approximately Mr 30,000 polypeptides, lacking hydrophobic or signal sequence that could facilitate transmembrane translocation and release of mature IL-1 (Mr 17,500). The current study utilizes an antiserum specific for murine IL-1 alpha in order to investigate membrane associated IL-1 alpha polypeptides and possible postsynthetic modifications of the IL-1 alpha precursor, that might account for its intracellular transport. Cell surface iodination of endotoxin stimulated murine macrophages allowed the detection of IL-1 molecules in size similar to the IL-1 alpha precursor (Mr 33,000). Membrane bound IL-1 alpha was sensitive to degradation by serine esterase activity to yield IL-1 peptides of Mr 16,000 to 18,000. Endotoxin stimulated macrophages, but not unstimulated cells, incorporated 32PO4 into the IL-1 alpha precursor. The phosphate label of the IL-1 alpha precursor is resistant to hydroxylamine and alkaline phosphatase treatment. Released IL-1 is not phosphorylated. Approximately 10% of the phosphorylated IL-1 alpha precursor is membrane bound and associated with fractions enriched in lysosomal vesicles. These data are consistent with a model for mIL-1 expression, in which pro IL-1 alpha is post-synthetically modified to achieve intracellular transport and further suggest that mIL-1 may be a prerequisite for the release of IL-1.
Mol Immunol 1988 Nov
PMID:Structure and function of membrane IL-1. 326 77

Three isozymes of carboxylesterase were purified from rat liver microsomes by using Sephadex G-150 gel filtration, DE-52 ion exchange, and chromatofocusing column chromatographies. These isozymes each showed a single protein band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were immunologically different from each other as determined by immunochemical blotting analysis and immunochemical inhibition of catalytic activity. The three isozymes were named RH1 (molecular weight 174,000, trimer, pl 6.0), RL1 (molecular weight 61,000, monomer, pl 6.5), and RL2 (molecular weight 61,000, monomer, pl 5.5). RL1 has the highest specific activities toward p-nitrophenylacetate and malathion. Acetanilide is a rather specific substrate for RL2, whereas RH1 has the highest specific activity for butanilicaine. RL1 has the highest specific activity for the hydrolysis of long-chain acyl-CoA. To investigate the hormonal regulation of carboxylesterase activities, we have quantitated RL1, RL2, and RH1 in liver microsomes from male and female rats using a radial immunodiffusion assay. The amount of RL1 in male rats was decreased by castration but recovered to almost the level in sham-operated rat liver microsomes after treatment of the castrated rats with testosterone. Conversely, in ovariectomized female rats, the amount of RL1 was increased as compared to that in sham-operated rats, and treatment of the ovariectomized rats with estradiol tended to decrease the quantity of RL1. In all cases of sex hormone treatment, the amount of RH1 remains unclear at present. However, the amount of RL2 may be, at least in part, regulated by estrogens. On the other hand, phenobarbital treatment of male and female rats caused a significant increase in the amounts of RH1 and RL2, whereas RL1 was not affected. It was concluded that the three isozymes differ considerably from each other in response to hormone treatment, inducibility, substrate specificity, and immunological properties.
Mol Pharmacol 1987 Jun
PMID:Multiplicity and regulation of hepatic microsomal carboxylesterases in rats. 360 Jun 3

C1 has been partially purified from serum and its ability to activate has been studied. The activation status of C1 was measured using a sensitive hemolytic assay which allowed the activation status of C1 in serum to be monitored. C1 did not activate in serum but would spontaneously activate when separated from certain other serum proteins, in particular, the C1-inhibitor protein. The activation of C1 was time and concn dependent, but addition of fully activated C1 did not affect either the rate or extent of activation. The activation of C1 could be inhibited reversibly by C1-inhibitor. This action of the C1-inhibitor was over and above its ability to regulate fully activated C1 by covalent bond formation with either the serine esterase of C1s or C1r. The results presented suggest that the C1-inhibitor plays a dual role in the regulation of C1 activation. The regulatory actions of C1-inhibitor would account for the presence of C1 in a zymogen form and for the episodic nature of complement consumption observed in individuals with genetic deficiencies of the C1-inhibitor protein.
Mol Immunol 1987 Jun
PMID:Regulation of the activation of C1 in serum. 365 2

A panel of clones of mink-Chinese hamster somatic cell hybrids was analysed to obtain data for assigning the genes for thymidine kinase-1 (TK1), galactokinase (GALK), subunit C of aldolase (ALDC), and esterase D (ESD) to specific mink chromosomes. The results demonstrate that the genes for TK1, GALK, ALDC and ESD are syntenic and located on mink chromosome 8. Prometaphase analysis of transformed mouse cells obtained by transfer of mink genes by means of metaphase chromosomes demonstrated the presence of mink chromosome 8 fragments of different sizes in some of the independent transformants. Segregation analysis of these fragments and mink TK1, GALK, ALDC and ESD allowed us to assign the genes for TK1 and GALK to 8p24, ALDC to pter-8p25, and ESD to 8q24-8qter.
Mol Gen Genet 1985
PMID:Regional assignment of the genes for TK1, GALK, ALDC, and ESD on chromosome 8 in the American mink by chromosome-mediated gene transfer. 386 31

Carboxylesterases (EC 3.1.1.1) of chicken brain were investigated by applying kinetic analysis of organophosphorus inhibition. By iterative elimination of exponential inhibition curves and by sequential inhibition experiments using a combination of two organophosphorus inhibitors, 11 different carboxylesterases of chicken brain were characterized with respect to their phenyl valerate-hydrolyzing activity (milliunits per gram of brain) and their inhibition by O,O-diethyl O-4-nitrophenyl phosphate (Paraoxon), O,O-diisopropylphosphorofluoridate, and N,N'-diisopropylphosphorodiamidic fluoride (Mipafox). The bimolecular inhibition rate constants (liters . mole-1 . min-1) were calculated for the 11 enzymes and 3 organophosphorus compounds. The corresponding data for acetylcholinesterase (EC 3.1.1.7) in chicken brain were determined. The importance of inhibition rate constants for the development of acute cholinergic symptoms, delayed neurotoxicity, and atypical organophosphate effects is shown.
Mol Pharmacol 1983 May
PMID:Inhibition of brain carboxylesterases by neurotoxic and nonneurotoxic organophosphorus compounds. 686 14

The membrane attack complex of human complement and its highly purified precursor proteins have been analyzed for phospholipase activity. Using three different sensitive assays, phospholipase A1, A2, C or D activity could not be detected. Based on the sensitivity of the assays employed, these results indicate the complement-mediated membrane damage is not enhanced by covalent breakdown of membrane phospholipids, but is entirely caused by physical action of the membrane attack complex. The results also imply that the putative serine esterase sites of C6 and C7 are not acting on phospholipids.
Mol Immunol 1983 Apr
PMID:The membrane attack complex of complement and its precursor proteins lack phospholipase activity. 686 55

A novel cultured cell line, P31/Fujioka, of monocytoid nature was established from leukemic cells in the peripheral blood of a seven-year-old boy with acute monoblastic leukemia. The P31/Fujioka cells have abundant cytoplasm, an indented nucleus of monocytoid appearance, pseudopods detectable by electron microscopy and alpha-naphthyl butyrate esterase activity which is completely inhibited by NaF, but they have no peroxidase activity. Immunologically, the P31/Fujioka cells possess Fc gamma-receptor and phagocytic activity towards sensitized erythrocytes (oxEAIgG), and are reactive with various monoclonal antibodies such as OKM1, anti-Mol, FMC10, FMC12 and OKI1. Chromosome analysis revealed the presence of marker chromosome 11q--due to Nos. 7; 11 translocation and No. 9 pericentric inversion. These findings indicate that the P31/Fujioka cells are derived from the patient's monoblastic leukemia cells and show a more distinct monocyte antigen than other known monocytoid cultured cell lines, U-937 and THP-1. The absence of Epstein-Barr virus nuclear antigen of this line was confirmed.
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PMID:A novel monocytoid cultured cell line, P31/Fujioka, derived from acute monoblastic leukemia. 696 83


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