Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synechocystis sp. PCC 6803 is capable of facultative photoheterotrophy with glucose as the sole carbon source. Eight mutants that were unable to take up glucose were transformed with plasmids from pooled gene banks of wild-type Synechocystis DNA prepared in an Escherichia coli vector that does not replicate in Synechocystis. One mutant (EG216) could be complemented with all gene banks to restore ability for photoheterotrophic growth. One of the gene banks was fractionated into single clones and plasmid DNA from each clone used to complement EG216. This yielded a 1.5 kb DNA fragment that was sequenced. It contained one complete open reading frame (gtr) whose putative gene product displayed high sequence conservation with the xylose transporter of E. coli and the mammalian glucose transporters. Further, the isolated gtr gene interrupted in vitro by a kanamycin resistance cassette could be used to construct mutants from wild-type Synechocystis sp. PCC 6803 that lacked a functional glucose transporter, thus confirming the identity of the gtr gene with the glucose transporter gene. This is the first prokaryotic glucose transporter known to share a sequence relationship with mammalian glucose transporters and the first sugar transporter from a cyanobacterium characterized at the sequence level.
Plant Mol Biol 1990 May
PMID:Sequence conservation among the glucose transporter from the cyanobacterium Synechocystis sp. PCC 6803 and mammalian glucose transporters. 212 97

Analysis of glucose transporter mRNA levels in adipose tissue from streptozotocin (STZ)-induced diabetic rats demonstrated a specific decrease (10-fold) in adipose tissue GLUT-4 mRNA with no significant effect on GLUT-1 mRNA levels. Treatment of STZ-diabetic rats with twice daily injections of insulin for 1-3 days resulted in a 16-fold increase in the relative amount of GLUT-4 mRNA to levels approximately 2-fold greater than those in control animals. However, after 7 days of insulin therapy the amount of GLUT-4 mRNA decreased approximately 2-fold back to the levels in the control animals. Normalization of the STZ-induced serum hyperglycemia by phlorizin treatment, which inhibits renal tubular reabsorption of glucose, had no effect on GLUT-4 mRNA in the absence of insulin. Similar to STZ-diabetes, fasting for 48 h also reduced adipose GLUT-4 mRNA levels. Parenteral administration of insulin with glucose over 7.5 h, but not glucose alone, increased the levels of the GLUT-4 mRNA 3- to 4-fold. These studies demonstrate that the relative glycemic state does not influence GLUT-4 glucose transporter mRNA expression in vivo and strongly suggests that insulin is a major factor regulating the levels of GLUT-4 mRNA in adipose tissue.
Mol Endocrinol 1990 Apr
PMID:Regulation of glucose transporter messenger RNA levels in rat adipose tissue by insulin. 214 65

When fibroblasts are transformed by the src oncogene, there is a two- to fivefold increase in glucose transport and in the level of immunoprecipitable glucose transporter protein. In chicken embryo fibroblasts (CEFs), this increase is correlated with a comparable reduction in the rate at which the glucose transporter protein is turned over. In contrast, in mammalian fibroblasts glucose transporter biosynthesis is increased by src, but there is little or no change in its turnover. To further understand the action of src on transporter turnover, we investigated whether a mammalian transporter can be stabilized by src in a chicken cell environment. The human type 1 glucose transporter protein (hGT), originally cloned from HepG2 cells, was expressed in CEFs or Rat-1 fibroblasts by using a retroviral vector. In CEFs transformed by a temperature-sensitive src mutant, tsNY68, turnover of hGT was lower at the permissive temperature (36 degrees C) than at the nonpermissive temperature (42 degrees C). When this protein was expressed in CEFs transformed by wild-type src, no difference in turnover was observed at the two temperatures. In the case of Rat-1 cells transformed by the temperature-sensitive src mutant tsLA29, turnover of hGT was the same at the permissive temperature (35 degrees C) as at the nonpermissive temperature (39.5 degrees C). These data demonstrate that a heterologous glucose transporter behaves in the same way in chicken and rat cells as the respective endogenous transporter, i.e., when src is active, the protein is stablilized against turnover in chicken cells but not in rat cells.
Mol Cell Biol 1990 Apr
PMID:The src oncogene can regulate a human glucose transporter expressed in chicken embryo fibroblasts. 215 35

Regulation of D-glucose transport in the porcine kidney epithelial cell line LLC-PK1 was examined. To identify the sodium-coupled glucose transporter (SGLT), we cloned and sequenced several partial cDNAs homologous to SGLT1 from rabbit small intestine (M. A. Hediger, M. J. Coady, T. S. Ikeda, and E. M. Wright, Nature (London) 330:379-381, 1987). The extensive homology of the two sequences leads us to suggest that the high-affinity SGLT expressed by LLC-PK1 cells is SGLT1. SGLT1 mRNA levels were highest when the D-glucose concentration in the culture medium was 5 to 10 mM. Addition of D-mannose or D-fructose, but not D-galactose, in the presence of 5 mM D-glucose suppressed SGLT1 mRNA levels. SGLT1 activity, measured by methyl alpha-D-glucopyranoside uptake, paralleled message levels except in cultures containing D-galactose. Therefore, SGLT1 gene expression may respond either to the cellular energy status or to the concentration of a hexose metabolite(s). By isolating several cDNAs homologous to rat GLUT-1, we identified the facilitated glucose transporter in LLC-PK1 cells as the erythroid/brain type GLUT-1. High-stringency hybridization of a single mRNA transcript to the rat GLUT-1 cDNA probe and failure to observe additional transcripts hybridizing either to GLUT-1 or to GLUT-2 probes at low stringency provide evidence that GLUT-1 is the major facilitated glucose transporter in this cell line. LLC-PK1 GLUT-1 mRNAs were highest at medium D-glucose concentrations of less than or equal to 2 mM. D-Fructose, D-mannose, and to a lesser extent D-galactose all suppressed GLUT-1 mRNA levels. Since the pattern of SGLT1 and GLUT-1 expression differed, particularly in low D-glucose or in the presence of D-galactose, we suggest that the two transporters are regulated independently.
Mol Cell Biol 1990 Dec
PMID:Regulation of glucose transporters in LLC-PK1 cells: effects of D-glucose and monosaccharides. 224 68

The characteristics of glucose transport by procyclic forms of Trypanosoma brucei were examined in a rapid transport assay using the glucose analogue 2-deoxyglucose. In contrast to bloodforms where the Km for 2-deoxyglucose transport is about 1 mM, procyclic forms have a Km of about 38 microM. Procyclic forms show temperature-dependent, saturable import, and import of 2-deoxyglucose is competitive with glucose and mannose. Unlike the bloodforms which employ facilitated diffusion, the procyclic forms actively transport glucose. Use of inhibitors and ionophores suggests that a protonmotive force is required for glucose transport in procyclic forms. Unlike the human erythrocyte glucose transporter, the glucose transporter of the T. brucei procyclic form is relatively insensitive to inhibition by cytocholasin B.
Mol Biochem Parasitol
PMID:Active transport of 2-deoxy-D-glucose in Trypanosoma brucei procyclic forms. 227 Jan 2

The SNF3 gene of Saccharomyces cerevisiae encodes a high-affinity glucose transporter that is homologous to mammalian glucose transporters. Point mutations affecting the function of the transporter were recovered from the genomes of four snf3 mutants and characterized. Two of the mutations introduced a charged amino acid into the first and second predicted membrane-spanning regions, respectively. The analogs of a bifunctional SNF3-lacZ fusion containing these two mutations were constructed, and the mutant fusion proteins were not localized to the plasma membrane, as judged by immunofluorescence microscopy. The third mutation produced a valine-to-isoleucine substitution in hydrophobic region 8, and the corresponding mutant fusion protein was correctly localized. The finding that this conservative change causes a transport defect is consistent with the possibility that this transmembrane region, which could exist as an amphipathic alpha-helix, forms part of the glucose channel through the membrane. The fourth snf3 allele harbored an ochre mutation midway through the coding sequence. We have also constructed mutations in the cloned SNF3 gene. A major difference between the yeast SNF3 protein and mammalian glucose transporters is the presence in the SNF3 protein of an additional 303 amino acids at the C terminus. Analysis of a series of C-terminal deletions and fusions to lacZ showed that this C-terminal region is important, but not essential, for transport function. We also report the genetic mapping of the SNF3 locus on the left arm of chromosome IV.
Mol Cell Biol 1990 Mar
PMID:Mutational analysis of the SNF3 glucose transporter of Saccharomyces cerevisiae. 240 60

The possibility that the glucose transporter may serve as water channel is explored with the help of theoretical and experimental arguments. A model for a pore is drawn based on a hypothetical water channel structure, subject to the constraints that: molecules will bind to the channel wall in successive rings, forming a hollow sleeve; an integer number of molecules will exist in each ring; the pore radius will not be large enough to allow water molecules along its center, but will be large enough to allow glucose molecules across. The only configurations that meet these conditions exhibit either 5 or 6 water molecules abreast in each ring, with pore radii of 4.1 and 4.5 A, respectively. The kinetic characteristics of such pores are estimated and found to conform to available evidence.
Mol Cell Biochem
PMID:On the possible permeation of water across the glucose transporter. 246 Jul 34

We report the functional expression of two different mammalian facilitative glucose transporters in Xenopus oocytes. The RNAs encoding the rat brain and liver glucose transporters were transcribed in vitro and microinjected into Xenopus oocytes. Microinjected cells showed a marked increase in 2-deoxy-D-glucose uptake as compared with controls injected with water. 2-Deoxy-D-glucose uptake increased during the 5 days after microinjection of the RNAs, and the microinjected RNAs were stable for at least 3 days. The expression of functional glucose transporters was dependent on the amount of RNA injected. The oocyte-expressed transporters could be immunoprecipitated with anti-brain and anti-liver glucose transporter-specific antibodies. Uninjected oocytes expressed an endogenous transporter that appeared to be stereospecific and inhibitable by cytochalasin B. This transporter was kinetically and immunologically distinguishable from both rat brain and liver glucose transporters. The uniqueness of this transporter was confirmed by Northern (RNA) blot analysis. The endogenous oocyte transporter was responsive to insulin and to insulinlike growth factor I. Most interestingly, both the rat brain and liver glucose transporters, which were not insulin sensitive in the tissues from which they were cloned, responded to insulin in the oocyte similarly to the endogenous oocyte transporter. These data suggest that the insulin responsiveness of a given glucose transporter depends on the type of cell in which the protein is expressed. The expression of hexose transporters in the microinjected oocytes may help to identify tissue-specific molecules involved in hormonal alterations in hexose transport activity.
Mol Cell Biol 1989 Oct
PMID:Functional expression of mammalian glucose transporters in Xenopus laevis oocytes: evidence for cell-dependent insulin sensitivity. 247 21

It has been shown previously that the rate of glucose transport in fibroblasts is accelerated by oncoproteins such as v-src, ras, and the transforming protein of feline sarcoma virus. This induction of glucose transport is associated with, and presumably caused by, induction of Hep-G2/rat brain glucose transporter gene expression. To determine the mechanism underlying the induction of glucose transporter gene expression by the v-src oncogene we studied cell lines that overexpress the normal counterpart of the v-src protein (c-src), or various mutants of the c-src protein. In these mutants, the tyrosines at positions 416, 527, or 519, or various combinations of these, have been replaced by phenylalanine by site directed mutagenesis, resulting in mutated c-src proteins that possess varying tyrosine kinase activity and transforming potential. Cells that overexpress the c-src protein show no changes in glucose transporter gene expression. However, when Tyr 527 in the COOH terminus of the c-src protein is replaced with Phe, the tyrosine kinase activity and transforming potential of the protein are increased and the protein acquires a potent ability to increase levels of glucose transporter mRNA and protein, as well as the rate of 2-deoxy-D-glucose uptake. This ability is abolished by the double mutation of Tyr to Phe in positions 416 and 527, which reduces the tyrosine kinase activity of the 527 single mutant. Thus, the ability of src proteins to induce expression of the glucose transport system is linked to the tyrosine kinase activity of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Nov
PMID:Relationship between c-src tyrosine kinase activity and the control of glucose transporter gene expression. 248 17

The effect of cAMP on glucose transport was studied in fibroblastic cells. Incubation of confluent NIH3T3 cells for 6 h in the presence of cholera toxin (10 ng/ml) and 3-isobutyl-1-methylxanthine [(IBMX) 0.2 mM] or 8-bromo-cAMP (0.3 mM) and IBMX resulted in a 4-fold increase in the rate of deoxyglucose uptake; no change in hexose transport could be detected after treatment for 30 min. Either cholera toxin (0.3 ng/ml-30 ng/ml) or 8-bromo-cAMP (30 microM-3 mM) increased the expression of the mRNA encoding the glucose transporter (GT) protein, as determined by hybridization of size-fractionated total RNA to a rat brain GT cDNA. Activation of adenylate cyclase by forskolin also rapidly induced a 4- to 10-fold increase in GT mRNA. The rise in the level of GT mRNA was maximal 3-4 h after addition of the drug, and returned to basal values by 16 h. The stimulation was concentration dependent, with forskolin producing a maximal effect at 30 microM. The effect of a submaximal concentration (1 microM) of forskolin was greatly enhanced in the presence of IBMX (0.2 mM), which alone had little effect on GT mRNA levels. The forskolin-stimulated increase in GT mRNA was not blocked by inhibition of protein synthesis by cycloheximide (10 micrograms/ml) or anisomycin (100 microM). The involvement of GT gene transcription was assessed by the nuclear run-on assay. Treatment of the cells with 30 microM forskolin increased transcription 10-fold within 30 min; the activation was not blocked by cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Sep
PMID:The regulation of glucose transporter gene expression by cyclic adenosine monophosphate in NIH3T3 fibroblasts. 248 19


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