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141.
The inactivation of the cytoplasmic domain of rat LAR, a receptor-like protein tyrosine phosphatase (PTPase), by iodoacetate and not by iodoacetamide suggested that iodoacetate interacts in a highly selective manner with the enzyme. The data indicate that iodoacetate binds at the active site of the enzyme with a stoichiometry of 0.8 mol of iodoacetate bound per mol of rat LAR. A single [14C]iodoacetate-labeled peptide was isolated following endoproteinase Lys-C digestion of the radiolabeled PTPase. Sequence analysis of the active site labeled peptide demonstrates that Cys-1522 contains the radiolabel. This residue has been shown by site-directed mutagenesis to be essential for rat LAR activity (Pot, D. A., Woodford, T. A., Remboutsika, E., Haun, R. S., and Dixon, J. E. (1991) J. Biol. Chem. 266, 19688-19696). Iodoacetate reacts only with the first domain of this double domain PTPase. These results, for the first time, directly identify the highly reactive cysteine residue at the active site of a PTPase and highlight the ability of this residue to participate as a nucleophile in the hydrolysis of phosphate from tyrosine. 相似文献
142.
John F. Dixon Chang Ho Lee Georgyi V. Los Lowell E. Hokin 《Journal of neurochemistry》1992,59(6):2332-2335
We previously reported that lithium, in the presence of acetylcholine, increased accumulations of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in brain cortex slices from the guinea pig, rabbit, rat, and mouse. In the mouse and rat, the Li(+)-induced increases required supplementation of the medium with inositol. This probably relates to the following facts: (a) Brain cortices of the mouse and rat contain in vivo concentrations of inositol half of that of the guinea pig. (b) Incubated rat brain cortex slices are depleted of inositol by 80%. (c) The slices require 10 mM inositol supplementation to restore in vivo concentrations. We now show that in monkey brain cortex slices, therapeutic concentrations of Li+ increase accumulation of inositol 1,4,5-trisphosphate. The inositol 1,3,4,5-tetrakisphosphate level is not increased. Neither inositol nor an agonist is required. The same effects are seen whether inositol 1,4,5-trisphosphate is quantified by the [3H]inositol prelabeling technique or by mass assay, although mass includes a pool of inositol 1,4,5-trisphosphate that is metabolically inactive. Thus, in a therapeutically relevant model for humans, Li+ increases inositol 1,4,5-trisphosphate levels in brain cortex slices, as was previously seen in lower mammals at non-rate-limiting concentrations of inositol. 相似文献
143.
S Furukawa N Sakata H N Ginsberg J L Dixon 《The Journal of biological chemistry》1992,267(31):22630-22638
We previously reported that treatment of Hep G2 cells with oleate significantly increased apolipoprotein B (apoB) secretion by reducing early intracellular degradation of nascent apoB. In the current study, inhibitors of secretory protein transport (brefeldin A and monensin), cell fractionation studies, and protease protection assays were utilized to determine the location of apoB degradation and to better define the mechanism whereby oleate treatment reduces nascent apoB intracellular degradation. When cells were treated with brefeldin A, which blocks endoplasmic reticulum (ER) to Golgi protein transport, apoB degradation continued in control cells, suggesting that apoB is degraded in the ER. When oleate-treated cells were blocked with brefeldin A, oleate failed to protect apoB from intracellular degradation. The effects of brefeldin A were not due to effects on lipid synthesis as brefeldin A did not inhibit the synthesis of triglyceride, phospholipid, free cholesterol, or cholesteryl ester in control cells and did not prevent the increases in triglyceride (14-fold) and phospholipid (1.4-fold) synthesis seen in oleate-treated cells. Simultaneous treatment of cells with brefeldin A and nocodazole, which inhibits retrograde transport of proteins from Golgi to ER, added to the evidence for the ER as the site of apoB degradation. This conclusion received further support from experiments in which cells were treated with monensin, a Na+ ionophore which halts protein secretion at the level of the trans-Golgi network. Early degradation of nascent apoB (between 10 and 20 min of chase) was observed in monensin-treated cells, but then cellular apoB degradation ceased and apoB was stable during the remaining chase period. More apoB accumulated in the Golgi of cells that had been treated with oleate and monensin. These results suggest that ER degradation occurs in monensin-treated cells, but then stops as apoB is transferred to the Golgi. The results obtained in whole cells were confirmed in studies using isolated ER and Golgi, which indicated that ER contains a proteolytic activity which degrades apoB, in vitro, whereas Golgi does not. ApoB degradation in isolated ER was not reduced by pretreatment with oleate. Finally, protease protection assays carried out with isolated microsomes indicated that a majority of the apoB in both control or oleate-treated HepG2 cells was located on the cytosolic side of the membranes.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
144.
Melanie E. M. Kelly S. Jeffrey Dixon Stephen M. Sims 《The Journal of membrane biology》1992,126(2):171-181
Summary Ionic conductances of rabbit osteoclasts were investigated using both whole-cell and cell-attached configurations of the patch-clamp recording technique. The predominant conductance found in these cells was an inwardly rectifying K+ conductance. Whole-cell currents showed an N-shaped current-voltage (I–13;V) relation with inward current activated at potentials negative to EK. When external K+ was varied, I-V curves shifted 53 mV/10-fold change in [K+]out, as predicted for a K+-selective channel. Inward current was blocked by Ba2+ and showed a time-dependent decline at negative potentials, which was reduced in Na+-free external solution. Inward single-channel currents were recorded in the cell-attached configuration. Single-channel currents were identified as inward-rectifier K+ channels based on the following observations: (i) Unitary I-V relations rectified, with only inward current resolved. (ii) Unitary conductance () was 31 pS when recorded in the cell-attached configuration with 140 mm K+ in the pipette and was found to be dependent on [K+]. (iii) Addition of Ba2+ to the pipette solution abolished single-channel events. We conclude that rabbit osteoclasts possess inwardly rectifying K+ channels which give rise to the inward current recorded at negative potentials in the whole-cell configuration. This inwardly rectifying K+ current may be responsible for setting the resting membrane potential and for dissipating electrical potential differences which arise from electrogenic transport of protons across the osteoclast ruffled border.This work was supported by The Arthritis Society and the Medical Research Council of Canada. M.E.M.K. was supported by a fellowship, S.J.D. a development Grant and S.M.S. a scholarship from the Medical Research Council. We thank Dr. Zu Gang Zheng for help with scanning microscopy. 相似文献
145.
146.
147.
Maurizio Rossetto Kingsley W. Dixon Eric Bunn 《In vitro cellular & developmental biology. Plant》1992,28(4):192-196
Summary Aeration of tissue cultured rare Australian plantsConostylis wonganensis S.D. Hopper (Haemodoraceae);Diplolaena andrewsii Ostenf.;Drummondita ericoides Harvey (Rutaceae);Eremophila resinosa F. Muell. (Myoporaceae);Eucalyptus ‘graniticola’ (Myrtaceae);Lechenaultia pulvinaris C. Gardner (goodeniaceae); andSowerbaea multicaulis E. Pritzel (Liliaceae) has been found to reduce vitrification in sensitive species as well as significantly improving shoot
quality and transfer to soil in most study species. A simple 7-mm hole with a double-layer insert of filter paper in the polypropylene
screw lids of the culture vessel decreased shoot vitrification over a 4-wk culture period. The method has implications for
facilitating the tissue culture of other rare Australian plants and reducing the occurrence of this developmental abnormality. 相似文献
148.
Crystallographic analysis of a complex between human immunodeficiency virus type 1 protease and acetyl-pepstatin at 2.0-A resolution 总被引:11,自引:0,他引:11
P M Fitzgerald B M McKeever J F VanMiddlesworth J P Springer J C Heimbach C T Leu W K Herber R A Dixon P L Darke 《The Journal of biological chemistry》1990,265(24):14209-14219
The mode of binding of acetyl-pepstatin to the protease from the human immunodeficiency virus type 1 (HIV-1) has been determined by x-ray diffraction analysis. Crystals of an acetyl-pepstatin-HIV-1 protease complex were obtained in space group P2(1)2(1)2 (unit cell dimensions a = 58.39 A, b = 86.70 A, c = 46.27 A) by precipitation with sodium chloride. The structure was phased by molecular replacement methods, and a model for the structure was refined using diffraction data to 2.0 A resolution (R = 0.176 for 12901 reflections with I greater than sigma (I); deviation of bond distances from ideal values = 0.018 A; 172 solvent molecules included). The structure of the protein in the complex has been compared with the structure of the enzyme without the ligand. A core of 44 amino acids in each monomer, including residues in the active site and residues at the dimer interface, remains unchanged on binding of the inhibitor (root mean square deviation of alpha carbon positions = 0.39 A). The remaining 55 residues in each monomer undergo substantial rearrangement, with the most dramatic changes occurring at residues 44-57 (these residues comprise the so-called flaps of the enzyme). The flaps interact with one another and with the inhibitor so as to largely preserve the 2-fold symmetry of the protein. The inhibitor is bound in two approximately symmetric orientations. In both orientations the peptidyl backbone of the inhibitor is extended; a network of hydrogen bonds is formed between the inhibitor and the main body of the protein as well as between the inhibitor and the flaps. Hydrophobic side chains of residues in the body of the protein form partial binding sites for the side chains of the inhibitor; hydrophobic side chains of residues in the flaps complete these binding sites. 相似文献
149.
Pattern of growth in weight of alate and apterous nymphs of the English grain aphid, Sitobion avenae
Daily increase in fresh weight was recorded for apterous and alate nymphs of S. avenae at 20°C. Comparison with a control group indicated that daily disturbance and weighing of nymphs did not affect significantly their growth, developmental time or survival. The increase in fresh weight of apterous and alate virginoparae at 20°C was best described by logistic equations. Alate virginoparae were significantly heavier than apterous virginoparae at birth and throughout most of their nymphal life, but they experienced a weight loss at the final ecdysis. The relative growth rate did not remain constant, but declined during development. The decline is associated with a decline in honeydew production per unit body weight. The implications of an inconstant relative growth rate and the marked loss in weight at the adult moult in alates are discussed.
Résumé L'enregistrement de l'augmentation quotidienne du poids frais à 20°C des larves ailées et aptères de S. avenae a montré que des perturbations quotidiennes n'affectent pas significativement la croissance, la durée du développement et la survie. Les équations logistiques décrivent plus exactement l'augmentation de poids frais des aptères et des ailés virginipares à 20°C. Les virginipares ailés étaient significativement plus lourds que les virginipares aptères à la naissance et pendant la plus grande partie de la vie larvaire, mais présentaient une perte de poids à la mue finale. Le taux de croissance relative ne restait pas constant, mais diminuait au cours du développement. La diminution était associée à une diminution de la production de miellat par unité de poids du corps. La discussion porte sur les conséquences de la variation de l'augmentation du poids relatif et de la perte marquée de poids à la mue imaginale.相似文献
150.
R.Dixon Phillips 《Analytical biochemistry》1981,113(1):102-107
A device is described which allows 12 samples to be prepared for acid hydrolysis in approximately 1 h. Screw-cap test tubes containing the weighed samples are placed into the apparatus along with 6 n HCl reagent. Air is removed rapidly and simultaneously from samples and reagent by alternate evacuation and nitrogen flushing. Reagent is measured into the sample tubes, and caps are threaded into place under a nitrogen atmosphere. 相似文献