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1.
Evidence for the subcellular localization and specificity of chlordane inhibition in the marine bacterium Aeromonas proteolytica. 总被引:2,自引:0,他引:2
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Sublethal levels (10 to 100 micrograms/ml) of the chlorinated insecticide chlordane (1,2,4,5,6,7,8,8-octachloro-3a,4,7,7a-tetrahydro-4,7-methanoindan) were introduced into the growth medium of the marine bacterium, Aeromonas proteolytica. Chlordane inhibited the synthesis of an extracellular endopeptidase by almost 40% but exhibited no such inhibition of the extracellular aminopeptidase also produced during the growth cycle. Studied with 14C-labeled chlordane demonstrated that the insecticide was not biologically degraded under the test conditions used and that up to 75% of the recoverable chlordane was cell associated within 48 h. Studied with uniformly labeled L[14C]valine and [2-14C]uracil established that neither the transport nor the incorporation of these protein and ribonucleic acid precursors was inhibited by chlordane. Separation of the membrane fractions using isopycnic centrifugation localized 14C-labeled chlordane in the cytoplasmic membrane. Also, chlordane inhibited the membrane-bound adenosine 5'-triphosphatase while the soluble (released) form of this enzyme remained unaffected. These data indicate that chlordane resides in the cytoplasmic membrane and may cause specific alterations in membrane-associated activities. 相似文献
2.
Silvia Penuela Alexander W Lohman Wesley Lai Laszlo Gyenis David W Litchfield Brant E Isakson Dale W Laird 《Channels (Austin, Tex.)》2014,8(2):124-130
The pannexin family of channel-forming proteins is composed of 3 distinct but related members called Panx1, Panx2, and Panx3. Pannexins have been implicated in many physiological processes as well as pathological conditions, primarily through their function as ATP release channels. However, it is currently unclear if all pannexins are subject to similar or different post-translational modifications as most studies have focused primarily on Panx1. Using in vitro biochemical assays performed on ectopically expressed pannexins in HEK-293T cells, we confirmed that all 3 pannexins are N-glycosylated to different degrees, but they are not modified by sialylation or O-linked glycosylation in a manner that changes their apparent molecular weight. Using cell-free caspase assays, we also discovered that similar to Panx1, the C-terminus of Panx2 is a substrate for caspase cleavage. Panx3, on the other hand, is not subject to caspase digestion but an in vitro biotin switch assay revealed that it was S-nitrosylated by nitric oxide donors. Taken together, our findings uncover novel and diverse pannexin post-translational modifications suggesting that they may be differentially regulated for distinct or overlapping cellular and physiological functions. 相似文献
3.
Phosphorylation of caldesmon77 by protein kinase C in vitro and in intact human platelets 总被引:1,自引:0,他引:1
Caldesmon is a widely distributed calmodulin- and actin-binding protein which occurs in different forms depending on the tissue or cell type under examination. On the basis of molecular weight, caldesmon species can be divided into two classes: caldesmon77 (Mr 70,000-80,000) and caldesmon150 (Mr 140,000-150,000). We have examined the phosphorylation of caldesmon77 by protein kinase C (the Ca2+/phospholipid-dependent enzyme) in vitro and in intact platelets. Caldesmon77, purified from bovine liver, could be phosphorylated by purified rat brain protein kinase C to a level of approximately 1.0 mol of phosphate per mol of caldesmon77 monomer. Two-dimensional tryptic peptide mapping and phosphoamino acid analysis reveals that caldesmon77 is phosphorylated at two major sites exclusively on serine residues. Following treatment of platelets with tumor-promoting phorbol ester, caldesmon77 phosphorylation was elevated 4-fold. Tryptic peptide mapping of phosphorylated platelet caldesmon77 demonstrates that phosphorylation is most significantly enhanced on two peptides which had migration patterns identical with those of the two major phosphopeptides of bovine liver caldesmon77 phosphorylated in vitro. The results of this study indicate that protein kinase C can phosphorylate caldesmon77 in vitro and in intact platelets, suggesting a role for protein kinase C in the regulation of caldesmon77 function or localization. 相似文献
4.
Microbiological Assay for Organic Compounds in Seawater. II: Distribution of Adenine, Uracil, and Threonine
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Biochemically deficient strains of Serratia marinorubra have been isolated with specific requirements for adenine, uracil, and threonine. Standard curves for dose to growth response have been obtained showing a linear sensitivity from 0.5 to 4.0 mg of adenine per liter of seawater, 0.1 to 2.0 mg of uracil per liter of seawater, and 0.5 to 10 mg of threonine per liter of seawater. These mutants have been used to test for the presence of their required metabolites in natural seawater samples from the Gulf of Mexico and adjacent bays. Of the three compounds under investigation, adenine was found in 10 samples, uracil in 2 samples, and threonine in none. The possible significance of these findings to the marine environment is discussed. 相似文献
5.
6.
Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans 总被引:13,自引:3,他引:10
Recent studies of mitochondrial DNA (mtDNA) variation in mammals and
Drosophila have shown an excess of amino acid variation within species
(replacement polymorphism) relative to the number of silent and replacement
differences fixed between species. To examine further this pattern of
nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5
genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans.
Of interest are the frequency spectra of silent and replacement
polymorphisms, and potential variation among genes and taxa in the
departures from neutral expectations. The Drosophila ND3 and ND5 data show
no significant excess of replacement polymorphism using the
McDonald-Kreitman test. These data are in contrast to significant
departures from neutrality for the ND3 gene in mammals and other genes in
Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however,
both Drosophila and human mtDNA show very significant excesses of amino
acid polymorphism. Silent polymorphisms at ND5 show a significantly higher
variance in frequency than replacement polymorphisms, and the latter show a
significant skew toward low frequencies (Tajima's D = -1.954). These
patterns are interpreted in light of the nearly neutral theory where mildly
deleterious amino acid haplotypes are observed as ephemeral variants within
species but do not contribute to divergence. The patterns of polymorphism
and divergence at charge-altering amino acid sites are presented for the
Drosophila ND5 gene to examine the evolution of functionally distinct
mutations. Excess charge-altering polymorphism is observed at the carboxyl
terminal and excess charge-altering divergence is detected at the amino
terminal. While the mildly deleterious model fits as a net effect in the
evolution of nonrecombining mitochondrial genomes, these data suggest that
opposing evolutionary pressures may act on different regions of
mitochondrial genes and genomes.
相似文献
7.
Molecular and Cellular Biochemistry - Casein kinase II is a protein serine/threonine kinase that is ubiquitously distributed in eukaryotes. Molecular cloning studies and protein sequence analysis... 相似文献
8.
D W Litchfield B Lüscher F J Lozeman R N Eisenman E G Krebs 《The Journal of biological chemistry》1992,267(20):13943-13951
In human epidermal carcinoma A431 cells, the beta subunit of casein kinase II is phosphorylated at an autophosphorylation site and at serine 209 which can be phosphorylated in vitro by p34cdc2 (Litchfield, D. W., Lozeman, F. J., Cicirelli, M. F., Harrylock, M., Ericsson, L. H., Piening, C. J., and Krebs, E. G. (1991) J. Biol. Chem. 266, 20380-20389). Given the importance of p34cdc2 in the regulation of cell cycle events, we were interested in examining the phosphorylation of casein kinase II during different stages of the cell cycle. In this study it is demonstrated that the extent of phosphorylation of serine 209 in the beta subunit is significantly increased relative to phosphorylation of the autophosphorylation site when chicken bursal lymphoma BK3A cells are arrested at mitosis by nocodazole treatment. This result suggests that serine 209 is a likely physiological target for p34cdc2. In addition, the alpha subunit of casein kinase II also undergoes dramatic phosphorylation with an associated alteration in its electrophoretic mobility when BK3A cells or human Jurkat cells are arrested with nocodazole. Phosphopeptide mapping studies indicate that p34cdc2 can phosphorylate in vitro the same peptides on the alpha subunit that are phosphorylated in cells arrested at mitosis. These phosphorylation sites were localized to serine and threonine residues in the carboxyl-terminal domain of alpha. Taken together, the results of this study indicate that casein kinase II is a probable physiological substrate for p34cdc2 and suggest that its functional properties could be affected in a cell cycle-dependent manner. 相似文献
9.
10.
Benjamin D. Stevens John Litchfield Jeffrey A. Pfefferkorn Karen Atkinson Christian Perreault Paul Amor Kevin Bahnck Martin A. Berliner Jessica Calloway Anthony Carlo David R. Derksen Kevin J. Filipski Mike Gumkowski Charanjeet Jassal Margit MacDougall Brendan Murphy Paul Nkansah John Pettersen Yan Zhang 《Bioorganic & medicinal chemistry letters》2013,23(24):6588-6592
Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties. 相似文献