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排序方式: 共有208条查询结果,搜索用时 15 毫秒
1.
Regulation of expression of a sheep metallothionein 1a-sheep growth hormone fusion gene in transgenic mice. 总被引:1,自引:0,他引:1 下载免费PDF全文
C M Shanahan N W Rigby J D Murray J T Marshall C A Townrow C D Nancarrow K A Ward 《Molecular and cellular biology》1989,9(12):5473-5479
Transgenic mice containing a sheep metallothionein 1a-sheep growth hormone fusion gene exhibited low, tissue-specific basal levels of transgene mRNA expression, resulting in slightly elevated levels of circulating growth hormone that did not lead to a detectable increase in growth. After zinc stimulation, high levels of transgene mRNA expression were induced in a number of tissues; these levels correlated with increased levels of circulating growth hormone, resulting in growth increases of up to 1.5 times the levels of controls and unstimulated transgenic mice. After removal of the zinc stimulus, transgene expression and circulating growth hormone concentrations returned to basal levels. Additional evidence from the pattern of developmental expression of the transgene suggests that zinc is the main regulator of this promoter in mice. The demonstrated regulation and low basal level of expression of the sheep metallothionein 1a promoter make it a candidate for use in other mouse transgenic studies and for use in transgenic livestock, in which regulation of expression is essential. 相似文献
2.
Identification of the glucose transporter in mammalian cell membranes with a 125I-forskolin photoaffinity label. 总被引:2,自引:1,他引:1 下载免费PDF全文
The glucose transporter has been identified in a variety of mammalian cell membranes using a photoactivatable carrier-free radioiodinated derivative of forskolin, 3-[125I]iodo-4-azidophenethylamido-7-O-succinyldeacetylforskoli n ([125I]IAPS-forskolin) at 1-3 nM. The membranes that were photolabelled with [125I]IAPS-forskolin were human placental membranes, rat cortical and cerebellar synaptic membranes, rat cardiac sarcolemmal membranes, rat adipocyte plasma membranes, smooth-muscle membranes, and S49 wild-type (WT) lymphoma-cell membranes. The glucose transporter in plasma membranes prepared from the insulin-responsive rat cardiac sarcolemmal cells, rat adipocytes and smooth-muscle cells were determined to be approx. 45 kDa by SDS/polyacrylamide-gel electrophoresis (PAGE). Photolysis of human placental membranes, rat cortical and cerebellar synaptic membranes, and WT lymphoma membranes with [125I]-IAPS-forskolin, followed by SDS/PAGE, indicated specific derivatization of a broad band (43-55 kDa) in placental membranes and a narrower band (approx. 45 kDa) in synaptic membranes and WT lymphoma membranes. Digestion of the [125I]IAPS-forskolin-labelled placental and WT lymphoma membranes with endo-beta-galactosidase showed a reduction in the apparent molecular mass of the radiolabelled band to approx. 40 kDa. The membranes that were photolabelled with [125I]IAPS-forskolin and trypsin-treated produced a radiolabelled proteolytic fragment with an apparent molecular mass of 18 kDa. [125I]IAPS-forskolin is a highly effective probe for identifying low levels of glucose transporters in mammalian tissues. 相似文献
3.
A panel of 12 Burkitt's lymphoma cell lines and four other B cell lines were tested for the presence of mutations in p53. Protein analysis using a mutant-specific antibody and sequencing of both cDNA and genomic DNA revealed changes relative to the standard p53 protein sequence in 12 of the 16 lines studied, including 10 of the BL lines. Mutation of p53 in the BL lines was usually accompanied by loss of the other allele of p53. Testing of the mutated p53 cDNAs for gain of transforming activity or loss of growth suppression activity showed that several of the BL mutants were functionally altered from wild-type p53. 相似文献
4.
Clark A. Lindgren Dennis J. Paulson Michael F. Shanahan 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1982,721(4):385-393
The usefulness of isolated Ca2+-tolerant myocytes as a cellular model system for investigating modulation of monosaccharide transport by insulin was investigated. We have found that the isolation technique described by Haworth et al. (Haworth, R.A., Hunter, D.R. and Berkoff, H.A. (1980) J. Mol. Cell. Cardiol. 12, 715–724), with some minor modifications, consistently gave the highest yield of quiescent, rod-shaped myocytes which maintained their integrity in the presence of 2 mM calcium. Using 3-O-methylglucose, a non-metabolized sugar, transport was shown to possess saturability, substrate stereospecificity, competition and countertransport; all of which have been thoroughly established for d-glucose transport in other systems. The apparent Km of transport ranged from 2.3 to 3.5 mM. Insulin (10 nM) caused a small but significant increase in Km and a 2–3-fold increase in Vmax. These results suggest that this myocyte preparation will provide a useful model for studying the transport-related effects of insulin as well as current hypotheses regarding the mechanism of insulin modulation of transport at the cellular level. 相似文献
5.
Christina M. Ridley Karen E. Thur Jessica Shanahan Nagendra Babu Thillaiappan Ann Shen Karly Uhl Charlotte M. Walden Ahad A. Rahim Simon N. Waddington Frances M. Platt Aarnoud C. van der Spoel 《The Journal of biological chemistry》2013,288(36):26052-26066
β-Glucosidase 2 (GBA2) is an enzyme that cleaves the membrane lipid glucosylceramide into glucose and ceramide. The GBA2 gene is mutated in genetic neurological diseases (hereditary spastic paraplegia and cerebellar ataxia). Pharmacologically, GBA2 is reversibly inhibited by alkylated imino sugars that are in clinical use or are being developed for this purpose. We have addressed the ambiguity surrounding one of the defining characteristics of GBA2, which is its sensitivity to inhibition by conduritol B epoxide (CBE). We found that CBE inhibited GBA2, in vitro and in live cells, in a time-dependent fashion, which is typical for mechanism-based enzyme inactivators. Compared with the well characterized impact of CBE on the lysosomal glucosylceramide-degrading enzyme (glucocerebrosidase, GBA), CBE inactivated GBA2 less efficiently, due to a lower affinity for this enzyme (higher KI) and a lower rate of enzyme inactivation (kinact). In contrast to CBE, N-butyldeoxygalactonojirimycin exclusively inhibited GBA2. Accordingly, we propose to redefine GBA2 activity as the β-glucosidase that is sensitive to inhibition by N-butyldeoxygalactonojirimycin. Revised as such, GBA2 activity 1) was optimal at pH 5.5–6.0; 2) accounted for a much higher proportion of detergent-independent membrane-associated β-glucosidase activity; 3) was more variable among mouse tissues and neuroblastoma and monocyte cell lines; and 4) was more sensitive to inhibition by N-butyldeoxynojirimycin (miglustat, Zavesca®), in comparison with earlier studies. Our evaluation of GBA2 makes it possible to assess its activity more accurately, which will be helpful in analyzing its physiological roles and involvement in disease and in the pharmacological profiling of monosaccharide mimetics. 相似文献
6.
RNA editing site recognition in higher plant mitochondria. 总被引:4,自引:0,他引:4
7.
Nesprin-1 and nesprin-2 (also known as Syne-1 and Syne-2,) are large ( approximately 3300-residue) vertebrate proteins associated with emerin and lamin A at the nuclear envelope of muscle cells and other cell types. We show that the previously described nesprins are short isoforms of giant proteins comprising an actin-binding amino-terminus connected to a carboxy-terminal klarsicht-related transmembrane domain by a massive ( approximately 6000-8000 amino acid) spectrin-like rod domain, making full-length nesprin-1, at one megadalton, the largest non-titin protein hitherto described in humans. We find that MSP-300, a 7000-residue Drosophila melanogaster protein whose disruption results in defects of muscle development, corresponds to the N-terminal two-thirds of the Drosophila nesprin ortholog. A nesprin-like protein is also encoded by the nematode genome. Moreover, we demonstrate that the larger isoforms of nesprin-1, like MSP-300, are localized to the sarcomeric Z-line of both skeletal and cardiac muscle. The recognition that a characteristic muscle-specific mutant phenotype in the fly results from a disruption of its nesprin ortholog reinforces the candidacy of the human proteins for involvement in genetic diseases of skeletal and cardiac muscle. 相似文献
8.
Boddy MN Lopez-Girona A Shanahan P Interthal H Heyer WD Russell P 《Molecular and cellular biology》2000,20(23):8758-8766
Cds1, a serine/threonine kinase, enforces the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. Cds1 is required for survival of replicational stress caused by agents that stall replication forks, but how Cds1 performs these functions is largely unknown. Here we report that the forkhead-associated-1 (FHA1) protein-docking domain of Cds1 interacts with Mus81, an evolutionarily conserved damage tolerance protein. Mus81 has an endonuclease homology domain found in the XPF nucleotide excision repair protein. Inactivation of mus81 reveals a unique spectrum of phenotypes. Mus81 enables survival of deoxynucleotide triphosphate starvation, UV radiation, and DNA polymerase impairment. Mus81 is essential in the absence of Bloom's syndrome Rqh1 helicase and is required for productive meiosis. Genetic epistasis studies suggest that Mus81 works with recombination enzymes to properly replicate damaged DNA. Inactivation of Mus81 triggers a checkpoint-dependent delay of mitosis. We propose that Mus81 is involved in the recruitment of Cds1 to aberrant DNA structures where Cds1 modulates the activity of damage tolerance enzymes. 相似文献
9.
BACKGROUND: There is concern that the aging of Canada''s population will strain our health care system. The authors address this concern by examining changes in the physician supply between 1986 and 1994 and by assessing the availability of physicians in 1994 relative to population growth and aging, and relative to supply levels in the benchmark province of Alberta. METHODS: Physician numbers were obtained from the Canadian Institute for Health Information. The amount of services provided by each specialty to each patient age group was analysed using Manitoba physician claims data. Population growth statistics were obtained from Statistics Canada. Age- and specialty-specific utilization data and age-specific population growth patterns were used to estimate the number and type of physicians that would have been required in each province to keep up with population growth between 1986 and 1994, in comparison with actual changes in the physician numbers. Physician supply in Alberta was used as a benchmark against which other provinces were measured. RESULTS: Overall, Canada''s physician supply between 1986 and 1994 kept pace with population growth and aging. Some specialties grew much faster than population changes warranted, whereas others grew more slowly. By province, the supply of general practitioners (GPs) grew much faster than the population served in New Brunswick (16.6%), Alberta (6.5%) and Quebec (5.3%); the GP supply lagged behind in Prince Edward Island (-5.4%). Specialist supply outpaced population growth substantially in Nova Scotia (10.4%), Newfoundland (8.5%), New Brunswick (7.3%) and Saskatchewan (6.8%); it lagged behind in British Columbia (-9.2%). Using Alberta as the benchmark resulted in a different assessment: Newfoundland (15.5%) and BC (11.7%) had large surpluses of GPs by 1994, whereas PEI (-21.1%), New Brunswick (-14.8%) and Manitoba (-11.1%) had substantial deficits; Quebec (37.3%), Ontario (24.0%), Nova Scotia (11.6%), Manitoba (8.2%) and BC (7.6%) had large surpluses of specialists by 1994, whereas PEI (-28.6%), New Brunswick (-25.9%) and Newfoundland (-23.8%) had large deficits. INTERPRETATION: The aging of Canada''s population poses no threat of shortage to the Canadian physician supply in general, nor to most specialist groups. The marked deviations in provincial physician supply from that of the benchmark province challenge us to understand the costs and benefits of variations in physician resources across Canada and to achieve a more equitable needs-based availability of physicians within provinces and across the country. 相似文献
10.
Cell nuclei spin in the absence of lamin b1 总被引:5,自引:0,他引:5
Ji JY Lee RT Vergnes L Fong LG Stewart CL Reue K Young SG Zhang Q Shanahan CM Lammerding J 《The Journal of biological chemistry》2007,282(27):20015-20026