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1.
Kinetics of uptake, retention, and radiotoxicity of 125IUdR in mammalian cells: implications of localized energy deposition by Auger processes 总被引:1,自引:0,他引:1
The kinetics of uptake, retention, and radiotoxicity of 125IUdR have been studied in proliferating mammalian cells in culture. The radioactivity incorporated into the DNA is directly proportional to the duration of incubation and to the extracellular concentration of 125I. The rate of proliferation of cells is related to the intracellular radioactive concentration and is markedly reduced at medium concentrations greater than or equal to 0.1 mu Ci/ml. At 37% survival the high LET type cell survival curve is characterized by an uptake of 0.035 pCi/cell, and the cumulated mean lethal dose to the cell nucleus is about 80 rad compared to 580 rad of X-ray dose for this cell line. The strong cytocidal effects of the decay of 125I correlate with localized irradiation of the DNA by the low energy Auger electrons. 相似文献
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Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. 总被引:302,自引:58,他引:244 下载免费PDF全文
Six monoclonal antibodies have been isolated from mice immunized with synthetic peptide immunogens whose sequences are derived from that of the human c-myc gene product. Five of these antibodies precipitate p62c-myc from human cells, and three of these five also recognize the mouse c-myc gene product. None of the antibodies sees the chicken p110gag-myc protein. All six antibodies recognize immunoblotted p62c-myc. These reagents also provide the basis for an immunoblotting assay by which to quantitate p62c-myc in cells. 相似文献
6.
Protein kinase C modulates in vitro phosphorylation of the smooth muscle heavy meromyosin by myosin light chain kinase 总被引:20,自引:0,他引:20
M Nishikawa J R Sellers R S Adelstein H Hidaka 《The Journal of biological chemistry》1984,259(14):8808-8814
Protein kinase C phosphorylates different sites on the 20,000-Da light chain of smooth muscle heavy meromyosin (HMM) than did myosin light chain kinase (Nishikawa, M., Hidaka, H., and Adelstein, R. S. (1983) J. Biol. Chem. 258, 14069-14072). Although protein kinase C incorporates 1 mol of phosphate into 1 mol of 20,000-Da light chain when either HMM or the whole myosin molecule is used as a substrate, it catalyzes the incorporation of up to 3 mol of phosphate/mol of 20,000-Da light chain when the isolated light chains are used as a substrate. Threonine is the major phosphoamino acid resulting from phosphorylation of HMM by protein kinase C. Prephosphorylation of HMM by protein kinase C decreases the rate of phosphorylation of HMM by myosin light chain kinase due to a 9-fold increase of the Km for prephosphorylated HMM compared to that of unphosphorylated HMM. Prephosphorylation of HMM by myosin light chain kinase also results in a decrease of the rate of phosphorylation by protein kinase C due to a 2-fold increase of the Km for HMM. Both prephosphorylations have little or no effect on the maximum rate of phosphorylation. The sequential phosphorylation of HMM by myosin light chain kinase and protein kinase C results in a decrease in actin-activated MgATPase activity due to a 7-fold increase of the Km for actin over that observed with phosphorylated HMM by myosin light chain kinase but has little effect on the maximum rate of the actin-activated MgATPase activity. The decrease of the actin-activated MgATPase activity correlates well with the extent of the additional phosphorylation of HMM by protein kinase C following initial phosphorylation by myosin light chain kinase. 相似文献
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The apparently negatively cooperative phosphorylation of smooth muscle myosin at low ionic strength is related to its filamentous state 总被引:4,自引:0,他引:4
The correlation curve between phosphorylation and MgATPase activity suggests that the 20,000-dalton light chain of both heads of a smooth muscle myosin or heavy meromyosin (HMM) molecule must be phosphorylated before the MgATPase activity of either head can be activated by actin. The two heads of HMM appear to be phosphorylated randomly at equal rates, while those of myosin are phosphorylated in a negatively cooperative manner (Persechini, A., and Hartshorne, D.J. (1981) Science, 213, 1383-1385; Ikebe, M., Ogihara, S., and Tonomura, Y. (1982) J. Biochem. 91, 1809-1812). We have investigated the cause of this difference between HMM and myosin. We find that if myosin is first phosphorylated at high ionic strength (0.6 M KCl), where it is monomeric, and then assayed for MgATPase activity (in 0.05 M KCl), the data support a model where the two heads are phosphorylated randomly with equal rates (i.e. similarly to HMM). The correlation curves between MgATPase activity and dephosphorylation of fully phosphorylated myosin, both in a filamentous and monomeric state, are also best explained by a model where dephosphorylation of one head is sufficient to deactivate the entire molecule. With monomeric myosin, the dephosphorylation appears to occur randomly with equal rates, whereas with filamentous myosin the dephosphorylation appears to be negatively cooperative. The correlation between dephosphorylation of HMM and its MgATPase activity is more complex and is consistent with a positively cooperative dephosphorylation. Direct analyses of the time courses of phosphorylation of HMM and monomeric myosin show that a single exponential is sufficient to fit the data through greater than 90% of the reaction. However, when phosphorylation is carried out at low ionic strength (0.02 M KCl), where myosin is present as filaments, the time course consists of two exponential functions where the rate constant for the phosphorylation of one myosin head is 6-10 times greater than that for the other head which is located on the same molecule. This suggests that when myosin is polymerized into filaments the two previously indistinguishable heads either become nonequivalent or are subject to head-head interactions leading to a negatively cooperative phosphorylation reaction. 相似文献
8.
A Mg2+-dependent phosphatase has been purified to apparent homogeneity from turkey gizzard smooth muscle. The enzyme has a Mr = 43,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 44,500 as determined by sedimentation equilibrium centrifugation under nondenaturing conditions. Using polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate all of the phosphatase activity was found to migrate as a single band, subsequently shown to have an Mr = 43,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is inactive in the absence of Mg2+ and maximum activity is reached at a free concentration of 12 mM Mg2+. Mn2+ can replace Mg2+, but the activity is only about one-fifth of that found with 12 mM Mg2+. NaF and the nucleotides ATP, ADP, and AMP inhibit phosphatase activity. This inhibition appears to be independent of their ability to bind Mg2+. The phosphatase purified from turkey smooth muscle appears to be identical with that purified from canine heart (Binstock, J. F., and Li, H. C. (1979) Biochem. Biophys. Res. Commun. 87, 1226-1234) and rat liver (Hiraga, A., Kikuchi, K., Tamura, S., and Tsuiki, S. (1981) Eur. J. Biochem. 119, 503-510). 相似文献
9.
C S Tsai S N Evan P J Asselberg R R McGregor D B Fowler 《The International journal of biochemistry》1983,15(11):1321-1328
Pyruvate kinase has been purified from codfish muscle. The ratio of phosphotransferase and oxalacetate decarboxylase activities remains relatively constant throughout purification steps. These two activities are dependent as well as sensitive to sulfhydryl reagents. In the presence of dithioerythritol, only one molecular form of pyruvate kinase is detected. However, the enzyme exists as four pseudoisozymes in the presence of 2-mercaptoethanol. The pseudoisozymes of codfish pyruvate kinase are interconvertible under the influence of sulfhydryl reagents. 相似文献
10.
Phosphorylation of smooth muscle heavy meromyosin by calcium-activated, phospholipid-dependent protein kinase. The effect on actin-activated MgATPase activity 总被引:14,自引:0,他引:14
Smooth muscle heavy meromyosin (HMM) can serve as a substrate for the Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) as well as for the Ca2+/calmodulin-dependent kinase, myosin light chain kinase. When turkey gizzard HMM is incubated with protein kinase C, 1.7-2.2 mol of phosphate are incorporated per mol of HMM, all of it into the 20,000-Da light chain of HMM. Two-dimensional peptide mapping following tryptic hydrolysis revealed that protein kinase C phosphorylated a different site on the 20,000-Da HMM light chain than did myosin light chain kinase. Moreover, sequential phosphorylation of HMM by myosin light chain kinase and protein kinase C resulted in the incorporation of 4 mol of phosphate/mol of HMM, i.e. 2 mol of phosphate into each 20,000-Da light chain. When unphosphorylated HMM was phosphorylated by myosin light chain kinase, its actin-activated MgATPase activity increased from 4 nmol to 156 nmol of phosphate released/mg of HMM/min. Subsequent phosphorylation of this phosphorylated HMM by protein kinase C decreased the actin-activated MgATPase activity of HMM to 75 nmol of phosphate released/mg of HMM/min. 相似文献