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1.
Two glucose transporters in Saccharomyces cerevisiae are glucose sensors that generate a signal for induction of gene expression. 总被引:11,自引:0,他引:11
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S Ozcan J Dover A G Rosenwald S W?lfl M Johnston 《Proceedings of the National Academy of Sciences of the United States of America》1996,93(22):12428-12432
Glucose is the preferred carbon source for most eukaryotic cells and has profound effects on many cellular functions. How cells sense glucose and transduce a signal into the cell is a fundamental, unanswered question. Here we describe evidence that two unusual glucose transporters in the yeast Saccharomyces cerevisiae serve as glucose sensors that generate an intracellular glucose signal. The Snf3p high-affinity glucose transporter appears to function as a low glucose sensor, since it is required for induction of expression of several hexose transporter (HXT) genes, encoding glucose transporters, by low levels of glucose. We have identified another apparent glucose transporter, Rgt2p, that is strikingly similar to Snf3p and is required for maximal induction of gene expression in response to high levels of glucose. This suggests that Rgt2p is a high glucose-sensing counterpart to Snf3p. We identified a dominant mutation in RGT2 that causes constitutive expression of several HXT genes, even in the absence of the inducer glucose. This same mutation introduced into SNF3 also causes glucose-independent expression of HXT genes. Thus, the Rgt2p and Snf3p glucose transporters appear to act as glucose receptors that generate an intracellular glucose signal, suggesting that glucose signaling in yeast is a receptor-mediated process. 相似文献
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Emerging evidence suggests a potential role of stearoyl-CoA desaturase (SCD)-1 in the control of body weight and energy homeostasis. The present study was conducted to investigate the effects of several energy balance-related factors (leptin, cerulenin, food deprivation, genotype, and gender) on SCD gene expression in chickens. In experiment 1, 6-week-old female and male broiler chickens were used. In experiment 2, two groups of 3-week-old broiler chickens were continuously infused with recombinant chicken leptin (8 micro g/kg/h) or vehicle for 6 h. In experiment 3, two groups of 2-week-old broiler chickens received i.v. injections of cerulenin (15 mg/kg) or vehicle. In experiment 4, two broiler chicken lines (fat and lean) were submitted to two nutritional states (food deprivation for 16 or 24 h and feeding ad libitum). At the end of each experiment, tissues were collected for analyzing SCD gene expression. Data from experiment 1 showed that SCD is ubiquitously expressed in chicken tissues with highest levels in the proventriculus followed by the ovary, hypothalamus, kidney, liver, and adipose tissue in female, and hypothalamus, leg muscle, pancreas, liver, and adipose tissue in male. Female chickens exhibited significantly higher SCD mRNA levels in kidney, breast muscle, proventriculus, and intestine than male chickens. However, hypothalamic SCD gene expression was higher in male than in female (P < 0.05). Leptin increased SCD gene expression in chicken liver (P < 0.05), whereas cerulenin decreased SCD mRNA levels in muscle. Both leptin and cerulenin significantly reduced food intake (P < 0.05). Food deprivation for either 16 or 24 h decreased the hepatic SCD gene expression in fat line and lean line chickens compared with their fed counterparts (P < 0.05). The hypothalamic SCD mRNA levels were decreased in both lines only after 24 h of food deprivation (P < 0.05). In conclusion, SCD is ubiquitously expressed in chickens and it is regulated by leptin, cerulenin, nutritional state, and gender in a tissue-specific manner. 相似文献
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Risheng Xu Bindu D. Paul Dani R. Smith Richa Tyagi Feng Rao A. Basit Khan Daniel J. Blech M. Scott Vandiver Maged M. Harraz Prasun Guha Ishrat Ahmed Nilkantha Sen Michela Gallagher Solomon H. Snyder 《Proceedings of the National Academy of Sciences of the United States of America》2013,110(40):16181-16186
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Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction. 总被引:20,自引:1,他引:20
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A D Yurochko D Y Liu D Eierman S Haskill 《Proceedings of the National Academy of Sciences of the United States of America》1992,89(19):9034-9038
Integrins are cell surface receptors found on monocytes that facilitate adhesion to both cellular and extracellular substrates. These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesis, we stimulated monocytes with monoclonal antibodies to different integrin receptors to specifically mimic the integrin receptor-ligand interactions. Engagement of the common beta chain of the beta 1 subfamily of integrins resulted in expression of the inflammatory mediator genes, interleukin 1 beta, interleukin 1 receptor antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas engagement of the common beta chain of the beta 2 family did not. Furthermore, to characterize integrin-mediated gene induction, we examined the ability of antibodies to the alpha chain of integrin receptors to regulate gene expression. Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of all the mediator genes. Receptor crosslinking was required because individual Fab fragments were unable to stimulate gene induction whereas the divalent F(ab')2 fragment and the whole IgG molecule could. Interleukin 1 beta secretion was dependent on the anti-integrin antibody used. Some antibodies required a second signal and, for others, direct engagement was sufficient for protein production. In conclusion, engagement of integrin receptors regulated the production of both inflammatory mediator mRNA and protein. These results suggest that integrin-dependent recognition and adherence may provide the key signals for initiation of the inflammatory response during monocyte diapedesis. 相似文献
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Thyroglobulin is a thyroid specific gene for the familial autoimmune thyroid diseases. 总被引:6,自引:0,他引:6
Yaron Tomer David A Greenberg Erlinda Concepcion Yoshiyuki Ban Terry F Davies 《The Journal of clinical endocrinology and metabolism》2002,87(1):404-407
The autoimmune thyroid diseases (AITDs) develop as a result of a complex interaction between predisposing genes and non-genetic factors. We have completed a whole genome scan in 56 families which revealed 7 major AITD loci (LOD scores >2), and additional minor loci (LOD scores >1). One of the minor loci was on chromosome 8q24 giving a maximum LOD score (MLS) of 1.8 at marker D8S284. This locus contained the thyroglobulin (Tg) gene which was a strong candidate gene for AITD. Because of this we analyzed the Tg gene region in detail using an expanded dataset of 102 families. The new linkage analysis showed stronger evidence for linkage at the Tg gene locus with an MLS of 3.5 between markers D8S514 and D8S284 (NPL = 2.0). We then proceeded to analyze the Tg gene directly. We identified a new microsatellite inside intron 27 of the Tg gene (designated Tgms2). Tgms2 showed strong evidence for linkage with AITD (MLS = 2.9), further suggesting that the Tg gene was linked to AITD. Association studies comparing 224 Caucasian AITD patients to 134 Caucasian controls showed an association of Tgms2 with AITD (p = 0.05, relative risk [RR] = 1.4). The association was stronger when only the probands from the linked families (n = 32) were used (p = 0.004, RR = 2.3). Transmission disequilibrium test (TDT) analysis also showed an association of Tgms2 with AITD (p = 0.02). We concluded therefore that the Tg gene was a major AITD susceptibility gene because it was both linked and associated with AITD. 相似文献
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The specific induction of myc protooncogene expression in normal human B cells is not a sufficient event for acquisition of competence to proliferate. 总被引:14,自引:3,他引:14
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E Smeland T Godal E Ruud K Beiske S Funderud E A Clark S Pfeifer-Ohlsson R Ohlsson 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(18):6255-6259
Resting human B cells can be activated to proliferate in the presence of both polyclonal antibodies to immunoglobulin mu heavy chains and B-cell growth factor (BCGF). This process appears to be temporally controlled in that the initial activation of the B cells and their responsiveness to BCGF is carried out by polyclonal anti-mu-chain antibodies alone. We have used this system to investigate the role of the c-myc gene in the cell cycle of normal human peripheral blood B cells. Our results show that the polyclonal anti-mu-chain antibody-induced B-cell activation is accompanied by a specific induction of c-myc gene expression without promoting subsequent entry into the S phase unless BCGF is added. Monoclonal antibodies to either mu chain or the pan-B-cell antigen Bp35 also revealed a similar G0-to-G1 transition and activation of c-myc gene expression. However, unlike activation with polyclonal anti-mu-chain antibodies, cells stimulated with these monoclonal antibodies do not acquire responsiveness to BCGF. The results imply that additional inducible functions must be present to potentiate the myc-specific function in order for the B cells to acquire the capacity to proliferate in response to BCGF. These findings are discussed in relation to the origin of B-cell malignancies. 相似文献
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腺病毒介导SARS病毒SN基因表达及其诱导的体液免疫 总被引:1,自引:0,他引:1
目的检测重组腺病毒Ad-SN在体内外的表达,初步探讨其在大鼠内诱导的体液免疫反应。方法Ad-SN感染Vero-E6细胞后用RT-PCR和WesternBlot法检测SN基因的表达;用WesternBlot法检测Ad-SN在大鼠皮下组织中的表达。Ad-SN皮下免疫大鼠,用ELISA法测定血清中抗SARS-CoVIgG水平。结果在Ad-SN感染的Vero-E6细胞中存在SN基因的转录,其mRNA量呈剂量依赖性;在Ad-SN感染的细胞、其培养上清及Ad-SN注射部位组织中均能检测到SN的表达。在Ad-SN免疫大鼠血清中可检测到高滴度SARS冠状病毒抗体(IgG)。结论Ad-SN能表达分泌型SN蛋白,并在大鼠体内诱导SARS-CoV特异的体液免疫反应。 相似文献
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The mechanisms whereby tissue sensitivity to PRL is controlled are not well understood. Here we report that expression of mRNA and protein for members of the SOCS/CIS/JAB family of cytokine signaling inhibitors is increased by PRL administration in ovary and adrenal gland of the lactating rat deprived of circulating PRL and pups for 24 h but not in mammary gland. Moreover, suckling increases SOCS mRNA in the ovary but not in the mammary gland of pup-deprived rats. Deprivation of PRL and pups for 48 h allows the mammary gland to induce SOCS genes in response to PRL administration, and this is associated with a decrease in basal SOCS-3 mRNA and protein expression to the level seen in other tissues, suggesting that SOCS-3 induced refractoriness related to filling of the gland. In reporter assays, SOCS-1, SOCS-3, and CIS, but not SOCS-2, are able to inhibit transactivation of the STAT 5-responsive beta-lactoglobulin promoter in transient transfection assays. Moreover, suckling results in loss of ovarian and adrenal responsiveness to PRL administered 2 h after commencement of suckling, as determined by STAT 5 gel shift assay. Immunohistochemistry was used to localize the cellular sites of SOCS-3 and CIS protein expression in the ovary and adrenal gland. We propose that induced SOCS-1, SOCS-3, and CIS are actively involved in the cellular inhibitory feedback response to physiological PRL surges in the corpus luteum and adrenal cortex during lactation, but after pup withdrawal, the mammary gland is rendered unresponsive to PRL by increased levels of SOCS-3. 相似文献
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Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation. 总被引:25,自引:1,他引:25
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K Todokoro R J Watson H Higo H Amanuma S Kuramochi H Yanagisawa Y Ikawa 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(23):8900-8904
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The prognostic value of Bcl-XL gene expression for remission induction is influenced by cytogenetics in adult acute myeloid leukemia. 总被引:3,自引:0,他引:3
BACKGROUND AND OBJECTIVES. There is growing evidence that altered expression of genes belonging to the BcL-2 family of apoptosis regulators might influence chemotherapy-induced apoptosis in malignant cells and therefore could confer multidrug resistance. So far expression studies of apoptosis-regulating genes on acute myeloid leukemia (AML) have mainly focused on Bcl-2 itself and most of them have not included other factors involved in drug resistance or apoptosis as parameters determining response to chemotherapy, disease progression and survival. DESIGN AND METHODS. We therefore examined Bcl-2, Bcl-XL and Bax gene expression in 235 adult patients with de novo or secondary myeloid leukemia. The expression levels were correlated with established prognostic factors such as age, cytogentic aberrations, mdr1 gene expression and clinical outcome in a multivariate analysis. RESULTS. Bcl-2 and Bcl-XL positive patients had a much lower white blood cell count than negative patients (p<0.001 and p=0.003, respectively). Bcl-2 expression correlated with FAB subtype M0 (p=0.03), Bax with M5b (p=0.02) and Bcl-XL with M6 (p=0.005). Mdr1 expression was more frequently seen in Bcl-2 and Bcl-XL positive patients (p=0.03 and p=0.02, respectively). Remarkably Bax was significantly less frequently expressed in de novo AML patients with high risk cytogenetics (p=0.007). No difference in expression was recognized for Bcl-2 or Bcl-XL when statistical analyses were done for cytogenetic risk groups. However, in the multivariate analysis regarding the group of de novo AML patients < or =60 years with intermediate risk cytogenetics, Bcl-XL expression was found to be an independent negative prognostic factor for response to induction therapy (p=0.04). In contrast, no prognostic impact of Bcl-XL expression on treatment response was seen within the group of patients with high risk cytogenetic findings. Neither Bcl-2 nor Bax nor Bcl-XL expression had a significant influence on overall or disease-free survival. INTERPRETATION AND CONCLUSIONS. These data indicate that the prognostic value of Bcl-XL gene expression for treatment response in AML patients < or =60 years is dependent on cytogenetics. 相似文献
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Biochemical evidence that secretor gene, Se, is a structural gene encoding a specific fucosyltransferase.
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T Kumazaki A Yoshida 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(13):4193-4197
Nonsecretors have no ABH blood group substances in their saliva and milk, but their erythrocytes contain the blood group substances. It has been generally believed that the secretor gene, Se, is a regulatory gene, not a structural gene, controlling the expression of (alpha 1----2)fucosyltransferase, which synthesizes the blood group H substance from its precursor, in secretions. To account for the existence of the blood type of "para Bombay" phenotype--i.e., H-negative in erythrocytes but H-positive in secretory fluids, another regulatory gene, Z, which would regulate the expression of the enzyme in the hematopoietic tissues, has been proposed. Contrary to this, a more simple model, in which the H gene and Se gene are both structural genes, encoding two separate fucosyltransferases in different tissues, was recently proposed. To settle the controversy, (alpha 1----2)fucosyltransferases were partially purified from human plasma and milk. The two enzymes differed from each other in the following respects: (i) the milk enzyme adsorbed to SP-Sephadex at pH 6.0, while the plasma enzyme did not; (ii) pH-activity profiles, with phenyl beta-D-galactoside as an acceptor, differed between the two enzymes; (iii) the milk enzyme exhibited lower thermal stability than the plasma enzyme; and (iv) Km values for several oligosaccharides with Gal(beta 1----3)GlcNAc and Gal(beta 1----4)GlcNAc as acceptors differed between the two enzymes. These results support the model that the Se gene is a structural gene encoding a distinctive (alpha 1----2)fucosyltransferase, refuting the classical regulatory gene model for the Se locus. The anomeric configuration of the fucosylated galactose residue produced by the action of enzyme was identified, thus establishing the specificity of the enzyme. 相似文献
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