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1.
S Miyatake T Yokota F Lee K Arai 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(2):316-320
We have isolated the mouse interleukin 3 (IL-3) gene from a mouse sperm DNA library based on homology with the mouse mast-cell growth-factor (MCGF) cDNA sequence. The nucleotide sequence determined for the gene and its flanking regions reveals that the IL-3 gene is composed of four introns and five exons. The nucleotide sequence of the exons agrees with that determined for the MCGF cDNA. A "TATA"-like sequence preceded by a G + C-rich region is found in the 5' flanking region. At the 3' region of the second intron are nine repeats of a closely related 14-base-pair (bp) sequence. These repeated sequences share extensive homology with a 20-bp repeated sequence found in the human genome, which was shown to have enhancer activity. Eight out of nine repeats form a 73-bp duplicated sequence and each 73-bp repeat contains sequences homologous to the core sequence suggested for enhancer elements. These sequences may play a role in the expression of the IL-3 gene in concanavalin A- or antigen-stimulated T lymphocytes. Stable transformants of L cells generated by co-transformation of the IL-3 gene with pSV2neo constitutively express MCGF activity indicating that the isolated gene is functional in vivo. 相似文献
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E Pringault S Robine D Louvard 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(23):10811-10815
We have isolated and characterized the complete human villin gene. The villin gene is located on chromosome 2q35-36 in humans and on chromosome 1 in mice. Villin belongs to a family of calcium-regulated actin-binding proteins that share structural and functional homologies. The villin gene is expressed mainly in cells that develop a brush border, such as mucosal cells of the small and large intestine and epithelial cells of the kidney proximal tubules. Villin gene expression is strictly regulated during adult life and embryonic development in the digestive and urogenital tracts and, thus, may be used as a marker of the digestive and renal cell lineages. The human villin gene has one copy per haploid genome, encompasses about 25 kilobases, and contains 19 exons. Analysis of the structural organization of this gene shows that the two mRNAs that encode villin in humans arise by alternative choice of one of the two polyadenylylation signals located within the last exon. The overall organization of the exons reflects the gene duplication event from which this family of actin-binding proteins originated. 相似文献
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A viral long terminal repeat in the interleukin 2 gene of a cell line that constitutively produces interleukin 2. 总被引:6,自引:3,他引:6
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S J Chen N J Holbrook K F Mitchell C A Vallone J S Greengard G R Crabtree Y Lin 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(21):7284-7288
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c-fos gene induction by interleukin 2: identification of the critical cytoplasmic regions within the interleukin 2 receptor beta chain. 总被引:3,自引:3,他引:0
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M Hatakeyama A Kawahara H Mori H Shibuya T Taniguchi 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(6):2022-2026
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O Wiborg L Berglund E Boel F Norris K Norris J F Rehfeld K A Marcker J Vuust 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(4):1067-1069
A gastrin gene was isolated from a genomic library of human DNA. The human gastrin gene is about 4100 base pairs long and contains two intervening sequences. Thus, a 3500-base-pair intervening sequence is located 5 base pairs proximal to the ATG initiator codon, while a 129-base-pair intervening sequence separates the region coding for the principal hormonal form of gastrin, the heptadecapeptide, from the region coding for the major amino-terminal portion of the gastrin precursor. The 5' flanking region of the gene contains the conserved sequences, T-A-T-A-A and G-A-C-T-C-A-T-A-T, in positions similar to those of other eukaryotic genes. 相似文献
11.
Chemical reduction of oxidized human lymphocytes inhibits interleukin 2 production but not induction of interleukin 2 responsiveness.
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E Roffman B Sredni A Smolinsky M Wilchek 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(16):5209-5213
Treatment with neuraminidase (NA) plus galactose oxidase (GalOxase) does not cause stimulation of human thymocytes. However, stimulation can be achieved by addition of exogenous interleukin 2 (IL-2). The IL-2-induced stimulation was inhibited with anti-Tac antibody, indicating that NA/GalOxase-oxidized cells can serve as inducers of functional IL-2 receptors on IL-2-responding T cells. The induction of IL-2 receptors by the oxidized cells was not inhibited by subsequent reduction with borohydride, since the cells could still be stimulated with IL-2. The presence of IL-2 receptors was also confirmed by flow cytometry using indirect immunofluorescence. Peripheral blood lymphocytes can be stimulated by NA/GalOxase treatment, and the conditioned medium from this treatment can support the growth of an IL-2-dependent line. This stimulation can be inhibited with borohydride and restored with IL-2. The conditioned medium derived from the borohydride-reduced cells cannot support the growth of the IL-2-dependent line, indicating that borohydride inhibits the oxidation-induced IL-2 production. The results suggest that NA/GalOxase-oxidized sites can be modified chemically without losing the potential to induce IL-2 receptors. 相似文献
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Localization in human interleukin 2 of the binding site to the alpha chain (p55) of the interleukin 2 receptor. 总被引:5,自引:3,他引:5
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K Sauvé M Nachman C Spence P Bailon E Campbell W H Tsien J A Kondas J Hakimi G Ju 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(11):4636-4640
Human interleukin 2 (IL-2) analogs with defined amino acid substitutions were used to identify specific residues that interact with the 55-kDa subunit (p55) or alpha chain of the human IL-2 receptor. Analog proteins containing specific substitutions for Lys-35, Arg-38, Phe-42, or Lys-43 were inactive in competitive binding assays for p55. All of these analogs retained substantial competitive binding to the intermediate-affinity p70 subunit (beta chain) of the receptor complex. The analogs varied in ability to interact with the high-affinity p55/p70 receptor. Despite the lack of binding to p55, all analogs exhibited significant biological activity, as assayed on the murine CTLL cell line. The dissociation constants of Arg-38 and Phe-42 analogs for p70 were consistent with intermediate-affinity binding; the Kd values were not significantly affected by the presence of p55 in binding to the high-affinity IL-2 receptor complex. These results confirm the importance of the B alpha-helix in IL-2 as the locus for p55-receptor binding and support a revised model of IL-2-IL-2 receptor interaction. 相似文献
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Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I. 总被引:75,自引:11,他引:75
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M Siekevitz M B Feinberg N Holbrook F Wong-Staal W C Greene 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(15):5389-5393
Cotransfection of cDNA encoding the trans-activator gene product of human T-cell leukemia virus, type I (HTLV-I) (tat-I), which acts in trans to augment viral gene expression, has revealed strong regulatory effects of this viral protein on the inducible cellular promoters governing human interleukin 2 (IL-2) and IL-2 receptor (Tac) gene expression. The tat-I protein stimulates a 3- to 6-fold increase in IL-2 receptor (Tac) promoter activity in transfected Jurkat T cells, but not in the natural killer-like YT cell line, as measured by changes in the expression of the chloramphenicol acetyltransferase (CAT; EC 2.3.1.28) reporter gene linked to this promoter. In contrast, tat-I alone has little or no effect on IL-2 promoter activity in Jurkat T cells but markedly synergizes with other mitogenic stimuli (phytohemagglutinin, phorbol 12-myristate 13-acetate, or the OKT3 monoclonal antibody), which alone are ineffective. The tat-I protein also partially circumvents the pronounced inhibitory effects of cyclosporin A on the IL-2 promoter. Other cellular and viral promoters are unaffected by the tat-I gene product, either alone or in combination with other mitogens. The specific effects of the tat-I gene product on the IL-2 and IL-2 receptor (Tac) promoters suggest the possibility of an autocrine or paracrine mechanism of T-cell growth as an early event in HTLV-I-mediated leukemogenesis. 相似文献
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R Bernards P F Little G Annison R Williamson R A Flavell 《Proceedings of the National Academy of Sciences of the United States of America》1979,76(10):4827-4831
We have constructed a physical map of the human G gamma-, A gamma-, delta-, and beta-globin genes. The previously described maps of the fetal and adult beta-like globin genes have been linked to one another by identification of a DNA fragment, generated by BamHI, that contains part of each of the A gamma- and delta-globin genes. The map obtained, which spans more than 40 kilobases, shows the following intergene distances: between G gamma and A gamma, 3500 base pairs; between A gamma and delta, 13,500 base pairs; and between delta and beta, 5500 base pairs. All genes are transcribed from the same DNA strand. 相似文献
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Structure of the human hexabrachion (tenascin) gene. 总被引:10,自引:0,他引:10
J R Gulcher D E Nies M J Alexakos N A Ravikant M E Sturgill L S Marton K Stefansson 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(21):9438-9442
The structure of the gene encoding human hexabrachion (tenascin) has been determined from overlapping clones isolated from a human genomic bacteriophage library. The genomic inserts were characterized by restriction mapping, Southern blot analysis, PCR, and DNA sequencing. The coding region of the hexabrachion gene spans approximately 80 kilobases of DNA and consists of 27 exons separated by 26 introns. The exon-intron structure supports a hypothesis based on the cDNA sequence that the hexabrachion gene is an assembly of DNA modules that are also found elsewhere in the genome. Single exons may encode a module, a portion of a module, or a group of modules. The 15 type III units similar to those found in fibronectin are each encoded either by a single exon or by two exons interrupted by an intron. All type III units known to be spliced out of the smaller forms of the protein are encoded by one exon. The fibrinogen-like domain of 210 amino acids is encoded by five exons. The 14.5 epidermal growth factor-like repeats are all encoded by a single exon. 相似文献
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Amino acid sequence and post-translational modification of human interleukin 2. 总被引:9,自引:4,他引:5
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R J Robb R M Kutny M Panico H R Morris V Chowdhry 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(20):6486-6490
Human interleukin 2 was separated into multiple molecular forms by selective immunoaffinity chromatography and chromatofocusing. For the most part, this heterogeneity was attributed to variations in glycosylation of the threonine residue in position 3 of the polypeptide chain. The various molecular forms of interleukin 2 had nearly identical specific activities in the in vitro proliferation assay, indicating that the glycosylation had no significant effect on this response. The entire primary sequence of interleukin 2, including the location of the intramolecular disulfide bridge, was determined by a combination of peptide mapping and protein sequencing. This information should aid in the determination of the active site(s) of the molecule. 相似文献
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Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization. 总被引:15,自引:5,他引:15
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L J Emorine S Marullo C Delavier-Klutchko S V Kaveri O Durieu-Trautmann A D Strosberg 《Proceedings of the National Academy of Sciences of the United States of America》1987,84(20):6995-6999
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Aoki Y Ichimura S Kikuchi T Yoshihara Y Kogawa M Tada N Nemoto K Fujikawa K 《The Journal of rheumatology》2005,32(2):320-324
OBJECTIVE: Osteoporosis is a major complication of chronic inflammatory diseases such as rheumatoid arthritis (RA). We describe disordered bone metabolism in transgenic mice that overexpress human interleukin 1a (hIL-1a). METHODS: Bone mineral density (BMD), microcomputed tomography (microCT), histomorphometry, and blood biochemical data of hIL-1a transgenic mice and littermate wild-type mice were examined. RESULTS: The femoral BMD of transgenic mice was decreased by 27.7% compared with wild-type mice. microCT revealed a marked reduction in the trabecular bone, and cortical thinning with an enlarged cavity was observed in femora of transgenic mice. Histomorphometric analysis revealed inhibition of several measures of bone formation, while the serum alkaline phosphatase level was reduced in transgenic mice; however, their indices of bone resorption were not elevated. CONCLUSION: Overexpression of hIL-1a causes osteopenia in mice. It was suggested that the systemic osteopenia in these transgenic mice occurred primarily as a result of decreased bone formation, with a reduction of bone mineralization rather than increased osteoclastic bone resorption. This may be one aspect of bone metabolism in RA that results in disease complications. 相似文献
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J D Siliciano T A Morrow S V Desiderio 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(23):11194-11198
T lymphocytes are activated by interactions with antigens, lymphokines, and cell adhesion molecules. Tyrosine phosphorylation has been implicated as important in signaling through each of these pathways, but except for p56lck, a member of the Src family that associates with CD4 and CD8, the protein-tyrosine kinases involved have not been defined. We describe here a tyrosine kinase gene that we have designated itk (for IL-2-inducible T-cell kinase). The itk gene specifies a 72-kDa protein-tyrosine kinase that is related to members of the Src family but lacks two features characteristic of Src kinases: an N-terminal myristoylation consensus sequence and a regulatory tyrosine residue near the C terminus. Analysis of mouse tissues and cell lines indicates that itk is specifically expressed in the T-cell lineage, suggesting that the tyrosine kinase encoded by itk functions in a signal transduction pathway unique to T lymphocytes. On addition of IL-2 to responsive T cells, itk RNA increases in parallel with that of IL-2R alpha, implicating itk in T-cell activation. 相似文献
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K Ashizawa S Yamashita T Tobinaga Y Nagayama H Kimura H Hirayu M Izumi S Nagataki 《Acta endocrinologica》1989,121(4):465-469