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11.
BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner. 总被引:40,自引:0,他引:40
BCR-ABL is a chimeric oncogene implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. BCR first exon sequences specifically activate the tyrosine kinase and transforming potential of BCR-ABL. We have tested the hypothesis that activation of BCR-ABL may involve direct interaction between BCR sequences and the tyrosine kinase regulatory domains of ABL. Full-length c-BCR as well as BCR sequences retained in BCR-ABL bind specifically to the SH2 domain of ABL. The binding domain has been localized within the first exon of BCR and consists of at least two SH2-binding sites. This domain is essential for BCR-ABL-mediated transformation. Phosphoserine/phosphothreonine but not phosphotyrosine residues on BCR are required for interaction with the ABL SH2 domain. These findings extend the range of potential SH2-protein interactions in growth control pathways and suggest a function for SH2 domains in the activation of the BCR-ABL oncogene as well as a role for BCR in cellular signaling pathways. 相似文献
12.
13.
Antigenic structure of histone H2B 总被引:3,自引:0,他引:3
S Muller M Couppez J P Briand J Gordon P Sautière M H van Regenmortel 《Biochimica et biophysica acta》1985,827(3):235-246
Antigenic determinants of histone H2B were localized using a series of 23 overlapping fragments of H2B obtained either by chemical and enzymatic cleavage of the histone or by solid-phase peptide synthesis. The ability of peptides to bind H2B antibodies was measured in an enzyme-linked immunosorbent assay, using antisera directed against calf thymus and chicken erythrocyte H2B as well as four anti H2B monoclonal antibodies obtained from autoimmune mice. Seven antigenic determinants were localized in the H2B molecule in the vicinity of residues 1-11, 6-18, 15-25, 26-35, 50-65, 94-113 and 114-125. Two of these determinants (residues 6-18 and 26-35) were revealed only through the binding properties of antibodies isolated from autoimmune mice. The usual correlation between hydrophilicity and antigenicity was found to hold for four of the epitopes, and the N- and C-termini of H2B were both antigenically active. 相似文献
14.
Quantitation of eukaryotic topoisomerase I reactivity with DNA. Preferential cleavage of supercoiled DNA 总被引:6,自引:0,他引:6
M T Muller 《Biochimica et biophysica acta》1985,824(3):263-267
A method has been used to quantitate the reaction between eukaryotic type I DNA topoisomerase and topological forms of DNA. This procedure (Trask, D.K., DiDonato, J.D. and Muller, M.T. (1984) Eur. Mol. Biol. Organ. J. 3, 671-676) measures the efficiency of DNA cleavage and concurrent formation of a covalent enzyme/DNA complex. Eukaryotic type I topoisomerases react preferentially by 5-10-fold with supercoiled DNA. The effect of supercoiling is clearly evident in that both the initial rate and final extent of the reaction is elevated. Because the dissociation rate is much lower than the association rate, it is possible to isolate native topoisomerase/DNA complexes. These complexes are comprised of enzyme molecules which are catalytically active when challenged with a second supercoiled DNA substrate. Collectively, the data support the conclusion that a functional intermediate in the reaction sequence is being detected and that the avian topoisomerase I preferentially cleaves supercoiled DNA. 相似文献
15.
This study presents experiments related to the role of solvent drag and solute drag in the transmembrane movement of nonelectrolytes in a perfused rat intestine preparation. Conditions were chosen to simulate the effects of luminal hyperosmolarity on the permeability of tracer solutes. Data are presented on net water flux, transepithelial potentials, and lumen-to-blood and blood-to-lumen tracer solute movements during control electrolyte perfusion and after making the perfusate hyperosmotic. The results indicate that both solvent drag and solute drag can play significant roles in the transepithelial movement of solute and solute permeabilities in the rat ileum preparation. It is suggested that the potential roles of solvent drag and solute drag should be accounted for or considered during the characterization of the mechanisms of biological membrane function. 相似文献
16.
Covalent cross-linking of vasoactive intestinal peptide (VIP) to its receptor in intact colonic adenocarcinoma cells in culture (HT 29) 总被引:1,自引:0,他引:1
J M Muller J Luis J Fantini B Abadie F Giannellini J Marvaldi J Pichon 《European journal of biochemistry》1985,151(2):411-417
[125I]Monoiodinated vasoactive intestinal peptide (125I-VIP) was cross-linked with human colonic adenocarcinoma cells (HT29 cells) grown as a monolayer using dithiobis(succinimidylpropionate) as cross-linking reagent. The cross-linked polypeptides were separated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. A major polypeptide of Mr = 67 000 was characterized and it behaved like a high-affinity binding site for VIP according to the following data. The concentration of native VIP (0.5 nM) giving half-maximum inhibition of 125I-VIP covalent cross-linking with this polypeptide was very similar to that giving half-maximum displacement of 125I-VIP on HT 29 cells (0.6 nM). Glucagon or insulin was unable to inhibit the labelling of the Mr-67 000 component. In our experimental conditions neither specific 125I-VIP binding nor covalent labelling was observed with monolayers of Madin Darby canine kidney epithelial cells (MDCK cells) or African green monkey kidney fibroblasts (Vero cells) while the Mr-67 000 polypeptide was also characterized with human rectal adenocarcinoma cells (HRT 18 cells), known to possess the VIP receptor. Preincubation of HT 29 cells with native VIP at 37 degrees C, before 125I-VIP binding and subsequent cross-linking reaction, decreased the labelling of the Mr-67 000 polypeptide up to 80%. Assuming one molecule of 125I-VIP cross-linked per polypeptide, we have characterized, for the first time, a major polypeptide of Mr = 64 000, which belongs to the high-affinity VIP binding site of an intestinal human cell line. 相似文献
17.
Internalization of the vasoactive intestinal peptide (VIP) in a human adenocarcinoma cell line (HT29) 总被引:4,自引:0,他引:4
J M Muller A el Battari E Ah-Kye J Luis F Ducret J Pichon J Marvaldi 《European journal of biochemistry》1985,152(1):107-114
The time course of internalization of radioiodinated vasoactive intestinal peptide (VIP) in HT29 cells was obtained using the technique of acetic acid removal of cell-surface-bound peptide. Even after 10 min incubation at 37 degrees C, 125I-VIP, initially bound on the HT29 cell surface, was compartmentalized within the cells. During the same time, degraded radioactive material was released by cells in the incubation medium. Localization of internalized 125I-VIP was investigated using two different subcellular fractionation techniques. 10 min after the onset of internalization, 125I-VIP labelling was found in intermediate structures and 10 min later the bulk of the radioactivity was detected in a low-density fraction containing very large lysosomes with a multivesicular aspect. The lysosomotropic agent NH4Cl appeared to inhibit 125I-VIP internalization, degradation and appearance of radiolabelled peptide in the large lysosomes in a time-dependent manner. Moreover, the effect of NH4Cl resulted in an accumulation of radioactive material in fractions containing microsomal structures. On the other hand, bacitracin, together with methylamine, highly enhanced 125I-VIP labelling in a membrane fraction, suggesting that these agents possibly act on a cell surface component of HT29 cells. These results support the conclusion that in HT29 cells, prelysosomal structures and large secondary lysosomes are probably part of the intracellular pathway of internalized VIP. 相似文献
18.
Internal antigen and immune network 总被引:5,自引:0,他引:5
H Kohler S Muller C Bona 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1985,178(2):189-195
The network hypothesis postulates the existence of internal idiotopic structures which mimic nominal antigens. Experimental evidence for idiotope internal antigen is presented and its implication for the Network hypothesis is discussed. The exploitation of the internal idiotope antigens (or preparation of vaccines) is a realistic possibility. 相似文献
19.
T S Gansler S Muller M P Cleary 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1985,180(1):155-162
The Zucker obese (fa/fa) rat is a model of hypertrophic/hyperplastic obesity. These rats develop marked hyperinsulinemia, insulin resistance, and pancreatic beta-cell hyperplasia. In the present study, chronic (22 weeks) administration of the 17-ketosteroid, dehydroepiandrosterone (DHEA), to obese Zucker rats significantly decreased body weight, and retroperitoneal and parametrial fat pad weights. In addition, beta-cell hyperplasia was reduced as well as pancreatic insulin content. DHEA treatment of lean Zucker rats also reduced body weight, fat depot weight, pancreatic islet diameter, and pancreatic insulin content. These data indicate that DHEA treatment appears to inhibit insulin synthesis and beta-cell proliferation. Whether this is due to a direct effect on the pancreas or due to improvement of peripheral insulin sensitivity remains to be elucidated. 相似文献
20.
A longitudinal, epidemiological study was carried out in a rural area of Kenya with a population of about 28,000 between 1974 and 1980. Population registration during this time showed that population growth was very high between 1974 and 1978 (4.4%/year) and much lower in 1979 and 1980 (1.1%). Natural increase was nearly as high as in Kenya as a whole (3.7%) in this period. Fertility was somewhat lower than in all Kenya (the crude birth rate was 46/1000) while mortality was substantially lower (7/1000). These rates are believed to be genuine and not due to under reporting of infant deaths. The most likely reason for these low infant mortality levels is the existence of favorable economic, social and hygienic conditions in the area compared to other parts of Kenya. The adult mortality rates are low too, in particular for the population aged 65 and over. The main reason is the overestimation of ages, in particular of women in the older age brackets, which has led to too large a denominator of the age specific rates in these age groups. Levels of temporary and permanent migration are high and probably characteristic for many parts of Kenya. Of the 19% of the registered population absent when visited by the fieldworkers, there were more males (23%) than females (14%). The % of absenteeism is higher for males between 20-59 years old, and also for females between 15 and 30. About 3% of the population is away for a short time, visiting relatives, attending weddings and funerals or occupied as traders. The large majority of absentees (14%) consists of temporary labor migrants and family members accompanying them. Many are gainfully employed in Nairobi and other towns in Kenya; some are farmers who seasonally move to another farm which they own outside the area. Others are wives and children who temporarily join their husbands, or polygamous men who are temporarily staying with another wife outside the area. All permanent movements to and from the study area, as well as within it, show that on average migration inwards and outwards balanced each other in the 7-year period. The gross migration rate is substantially higher for females than for males. This is due to family related reasons: marriage, divorce, separation. Other categories of migrants are those families who establish a new business or farm elsewhere, teachers and pastors who are transferred, and farm laborers, housemaids and servants. Poor economic conditions of 1979/80, due to a drop in coffee prices and poor harvests of coffee, maize and beans, led to more emigration and less immigration. 相似文献