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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trypanosoma brucei is a unicellular parasite that is transmitted from one mammalian host to the next by tsetse flies. The expression of many trypanosome genes is regulated during the life cycle but there is no evidence for developmental control of transcription by RNA polymerase II. T. brucei expresses at least two hexose transporter mRNAs that are developmentally regulated; we show here that specific portions of the 3'-untranslated regions are responsible for the differential expression. Different trypanosome 3'-untranslated regions, from surface protein, phosphoglycerate kinase and aldolase genes as well as the hexose transporter genes, conferred a spectrum of levels of reporter gene expression, and these activities differed between bloodstream forms and the procyclic forms that replicate in the tsetse vector. Experiments with permanently transformed cell lines showed that regulation occurs at the mRNA level. The results suggest that post-transcriptional control of mRNAs in trypanosomatids operates at several levels, and that it will not always be possible to attribute all the regulation to short RNA motifs.
Mol Biochem Parasitol 1995 Dec
PMID:Role of 3'-untranslated regions in the regulation of hexose transporter mRNAs in Trypanosoma brucei. 872 Jan 70

A novel insulin-secreting cell line, BRIN-BD11, was recently established following electrofusion of RINm5F cells with NEDH rat pancreatic islet cells. In the present study, D-glucose metabolism was compared in BRIN-BD11 and RINm5F cells. The concentration dependency of D[5-3H]glucose utilization displayed a comparable pattern in the two cell lines, but the absolute values were lower in BRIN-BD11 than RINm5F cells. Except in the case of D-[1-14C]glucose, the ratio between 14C labeled D-glucose oxidation and D-[5-3H]glucose utilization was higher, however, in BRIN-BD11 than RINm5F cells. Moreover, BRIN-BD11 cells were less affected than RINm5F cells by a rise in D-glucose concentration, in terms of the inhibitory action of the hexose upon oxidative variables, such as oxidative glycolysis, pyruvate decarboxylation, and oxidation of glucose-derived acetyl residues in the Krebs cycle. The total energy yield from D-glucose catabolism appeared similar, however, in BRIN-BD11 and RINm5F cells. These findings extend the knowledge that BRIN-BD11 cells display an improved metabolic and secretory behavior, when considering the difference otherwise found between normal and tumoral islet cells.
Biochem Mol Med 1996 Apr
PMID:D-glucose metabolism in BRIN-BD11 islet cells. 873 87

Isolated rat pancreatic islet B-cells loaded with the Ca2(+)-sensitive fluorochrome Fluo-3 were examined by single-step flow cytometry at increasing concentrations of D-glucose (1.0 to 20.0 mM). The near forward scatter of light was unaffected by changes in hexose concentration. The Fluo-3 fluorescent signal slightly decreased when the glucose concentration was raised from 1.0 to 5.0 mM, and progressively increased at higher hexose concentrations. The fluorescence attributable to endogenous NAD(P)H increased dramatically throughout the full range of D-glucose concentration, with a typical sigmoidal concentration-response relationship. No evidence for a bimodal frequency distribution of these variables was found, whether at low or high D-glucose concentrations. The dispersion of individual NAD(P)H measurements, as judged by either their coefficient of variation or the height of their modal peak, was less pronounced at high than at low D-glucose concentrations. These findings document vastly different concentration-response relationships for metabolic and ionic variables in glucose-stimulated B-cells. They confirm that all B-cells do not display an identical behavior, but argue against the existence of subpopulation heterogeneity in their responsiveness to D-glucose.
Mol Cell Endocrinol 1996 Apr 19
PMID:Pancreatic islet B-cell individual variability rather than subpopulation heterogeneity. 873 2

A chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP), induced an acidification of cytosol by about 0.05 pH units in 30 sec followed by an alkalinization in human neutrophils. The quantitative contribution of acid production to the acidification was studied. The superoxide (O2-) production stimulated by fMLP was not involved in the acidification because the production of acids in neutrophils from patients with chronic granulomatous disease who do not produce O2-, was the same as that in normal neutrophils. The intracellular acidification was completely inhibited by deoxyglucose, suggesting that energy metabolism enhanced upon stimulation by fMLP might be the main source of the acidification. Although enhancement of the lactate formation by fMLP was 0.8 nmol/10(6) cells, which could lower intracellular pH by 0.08 pH units, the lactate production could not explain the initial acidification because the production of lactate started at 1 min after the stimulation while the intracellular acidification began immediately after the stimulation. Mitochondrial respiratory inhibitors such as KCN and rotenone had no effects on the fMLP-induced intracellular acidification. The fMLP-induced production of CO2 in 30 sec through the hexose monophosphate shunt was only 2.6 pmol/10(6) cells, which was calculated to decrease intracellular pH by only 0.0014. Thus, changes of energy metabolism induced by fMLP does not explain the acidification.
Mol Cell Biochem 1995 Nov 22
PMID:Quantitative contribution of the acid production to the intracellular acidification in human neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine. 875 Nov 62

The transcription of the yeast FBP1 and PCK1 genes, which encode the gluconeogenic enzymes fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, is repressed by glucose. Here, we show that this repression is both very strong and exceptionally sensitive to glucose, being triggered by glucose at concentrations less than 0.005% (0.27 mM). This repression remains operative in yeast mutants carrying any one of the three hexose kinases, but is lost in a triple hxk1, hxk2, glk1 mutant. In addition, 2-deoxyglucose can trigger the repression, but 6-deoxyglucose cannot, suggesting that internalization and phosphorylation of the glucose is essential for repression to occur. While gluconeogenic gene transcription is subject to the Mig 1p-dependent pathway of glucose repression, the exquisite response to glucose is maintained in hxk2 and mig1 mutants, suggesting that this pathway is not essential for the response. The response can also be triggered by the addition of exogenous cAMP, suggesting that the Ras/cAMP pathway can mediate repression of the FPB1 and PCK1 mRNAs. However, the response is not dependent upon this pathway because it remains intact in Ras, adenyl cyclase and protein kinase A mutants. The data show that yeast cells can detect very low glucose concentrations in the environment, and suggest that several distinct signalling pathways operate to repress FPB1 and PCK1 transcription in the presence of glucose.
Mol Microbiol 1996 May
PMID:Multiple signalling pathways trigger the exquisite sensitivity of yeast gluconeogenic mRNAs to glucose. 879 72

We have identified a new gene, PFK27, that encodes a second inducible 6-phosphofructo-2-kinase in the yeast Saccharomyces cerevisiae. Sequencing shows an open reading frame of 397 amino acids and 45.3 kDa. Amino acid sequence comparisons with other bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoenzymes of various organisms revealed similarities only to the kinase domains. Expression of PFK27 was induced severalfold by glucose and sucrose, but not by galactose or maltose, suggesting that sugar transport might be involved in triggering the induction signal. We have constructed a mutant strain devoid of any fructose-2,6-bisphosphate. The mutant strain grew well on several kinds and concentrations of carbon sources. The levels of hexose phosphates in the cells were increased, but flux rates for glucose utilization and ethanol production were similar to the wild-type strain. However, after the transfer of the mutant cells from respiratory to fermentative growth conditions, growth, glucose consumption and ethanol production were delayed in a transition phase. Our results show that fructose-2,6-bisphosphate is an important effector in vivo of the 6-phosphofructo-1-kinase/fructose-1 ,6-bisphosphatase enzyme pair, and is involved in the initiation of glycolysis during the transition to a fermentative mode of metabolism. Nevertheless, it can be effectively replaced by other effectors and regulatory mechanisms during growth on glucose.
Mol Microbiol 1996 Apr
PMID:Cloning of a second gene encoding 5-phosphofructo-2-kinase in yeast, and characterization of mutant strains without fructose-2,6-bisphosphate. 886 Dec 5

The RGT1 gene of Saccharomyces cerevisiae plays a central role in the glucose-induced expression of hexose transporter (HXT) genes. Genetic evidence suggests that it encodes a repressor of the HXT genes whose function is inhibited by glucose. Here, we report the isolation of RGT1 and demonstrate that it encodes a bifunctional transcription factor. Rgt1p displays three different transcriptional modes in response to glucose: (i) in the absence of glucose, it functions as a transcriptional repressor; (ii) high concentrations of glucose cause it to function as a transcriptional activator; and (iii) in cells growing on low levels of glucose, Rgt1p has a neutral role, neither repressing nor activating transcription. Glucose alters Rgt1p function through a pathway that includes two glucose sensors, Snf3p and Rgt2p, and Grr1p. The glucose transporter Snf3p, which appears to be a low-glucose sensor, is required for inhibition of Rgt1p repressor function by low levels of glucose. Rgt2p, a glucose transporter that functions as a high-glucose sensor, is required for conversion of Rgt1p into an activator by high levels of glucose. Grr1p, a component of the glucose signaling pathway, is required both for inactivation of Rgt1p repressor function by low levels of glucose and for conversion of Rgt1p into an activator at high levels of glucose. Thus, signals generated by two different glucose sensors act through Grr1p to determine Rgt1p function.
Mol Cell Biol 1996 Nov
PMID:Rgt1p of Saccharomyces cerevisiae, a key regulator of glucose-induced genes, is both an activator and a repressor of transcription. 888 70

Most or all mammalian cells contain vanadium at a concentration of 0.1-1.0 microM. The bulk of the vanadium in cells is probably in the reduced vanadyl (IV) form. Although this element is essential and should be present in the diet in minute quantities, no known physiological role for vanadium has been found thus far. In the years 1975-1980 the vanadate ion was shown to act as an efficient inhibitor of Na+,K(+)-ATPase and of other related phosphohydrolyzes as well. In 1980 it was observed that vanadate vanadyl, when added to intact rat adipocytes, mimics the biological actions of insulin in stimulating hexose uptake and glucose oxidation. This initiated a long, currently active, field of research among basic scientists and diabetologists. Several of the aspects studied are reviewed here.
Mol Cell Biochem
PMID:Insulin-like actions of vanadate are mediated in an insulin-receptor-independent manner via non-receptor protein tyrosine kinases and protein phosphotyrosine phosphatases. 892 46

We show that cells deleted for SNF3, HXT1, HXT2, HXT3, HXT4, HXT6, and HXT7 do not take up glucose and cannot grow on media containing glucose as a sole carbon source. The expression of Hxt1, Hxt2, Hxt3, Hxt6, or Gal2 in these cells resulted in glucose transport and allowed growth on glucose media. In contrast, the expression of Snf3 failed to confer glucose uptake or growth on glucose. HXT6 is highly expressed on raffinose, low glucose, or nonfermentable carbon sources but is repressed in the presence of high concentrations of glucose. The maintenance of HXT6 glucose repression is strictly dependent on Snf3 and not on intracellular glucose. In snf3 delta cells expression of HXT6 is constitutive even when the entire repertoire of HXT genes is present and glucose uptake is abundant. In addition, glucose repression of HXT6 does not require glucose uptake by HXT1, HXT2, HXT3 or HXT4. We show that a signal transduction pathway defined by the Snf3-dependent hexose regulation of HXT6 is distinct from but also overlaps with general glucose regulation pathways in Saccharomyces cerevisiae. Finally, glucose repression of ADH2 and SUC2 is intact in snf3 delta hxt1 delta hxt2 delta hxt3 delta hxt4 delta hxt6 delta hxt7 delta gal2 cells, suggesting that the sensing and signaling mechanism for general glucose repression is independent from glucose uptake.
Mol Biol Cell 1996 Dec
PMID:A novel signal transduction pathway in Saccharomyces cerevisiae defined by Snf3-regulated expression of HXT6. 897 Jan 57

Two different spontaneous glucose transport (GLUT) mutants were used to examine the identity and properties of proteins involved in rat cardiac myoblast glucose transport processes. The parental clone, H9C2, possessed a high (HAHT) and a low (LAHT) affinity hexose transport process, and the GLUT 1, 3 and 4 isoforms. Mutant RCM was devoid of HAHT, the GLUT 3 transcript, and a 41 kDa protein recognizable by an anti-mouse GLUT 3 Ab. Mutant EZ-4 was impaired in the GLUT 3 and 4 isoforms, and in HAHT and LAHT. These studies demonstrated a close association of the GLUT 3 and 4 isoforms with the HAHT and LAHT processes, respectively. Both GLUT 3 and 4 isoforms were regulated in opposite ways during myogenesis, and both GLUT 3 mutants were impaired in myogenesis. Despite its normal GLUT 1 transcript level, mutant EZ-4 was devoid of an efficient carrier-mediated glucose transport process, thus suggesting that the GLUT 1 transporter was inoperative in rat cardiac myoblasts. Unlike the rat skeletal. L6 GLUT 1 isoform, expression of the rat cardiac GLUT 1 isoform was not affected by glucose starvation, and was not reduced in multinucleated myotubes. These studies demonstrated the usefulness of transport mutants in determining the identity, expression and property of GLUT isoforms and their association with specific transport processes.
Biochem Mol Biol Int 1997 Jan
PMID:Use of transport mutants to examine the identity and expression of GLUT isoforms in rat cardiac myoblasts. 904 40


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