Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastrin gene is expressed in fetal pancreatic islet cells, but in the adult is expressed mainly in the gastric antrum. To study the regulation of the gastrin promoter, we created several transgenes containing the human and rat gastrin 5' flanking regions joined to the coding sequences of the human gastrin gene. The human gastrin transgene contained 1,300 bp of 5' flanking DNA, while the rat gastrin transgene contained 450 bp of 5' flanking DNA. The human gastrin transgene was expressed in fetal islets, but was not expressed in adult gastric antrum. In contrast, the rat gastrin transgene was expressed in adult antral G cells, but no expression was observed in fetal islets. To study the possible role of gastrin as an islet growth factor, a chimeric insulin-gastrin (INS-GAS) transgene was created, in which the expression of the human gastrin gene is driven from the rat insulin I promoter. These INS-GAS mice were mated with mice overexpressing TGF alpha, transcribed from a mouse metallothionein-transforming growth factor alpha (MT-TGF alpha) transgene. While overexpression of gastrin or TGF alpha alone had no effect on islet mass, overexpression of both transgenes resulted in a twofold increase in islet mass. In conclusion, these data indicate that (1) gastrin can interact synergistically with TGF alpha to stimulate islet growth; (2) the human gastrin transgene contains the islet specific enhancer; (3) the rat gastrin transgene contains the antral specific enhancer.
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PMID:Function and regulation of gastrin in transgenic mice: a review. 134 Oct 73

Streptococcus pyogenes (group A streptococci; GAS) expresses important virulence factors like the antiphagocytic M protein, the complement factor-inactivating C5a peptidase and the immunoglobulin-Fc-binding proteins on its surface. The corresponding emm, scpA, and emm-related (fcrA, ennX) genes are adjacently encoded on the genome. They are coordinately in trans regulated by the positive regulatory VirR factor. The responsible virR gene is also located within this segment of the genome which was called vir-regulon. There are at least three different types of organization of the vir-regulon. A frequently encountered type is the "Large vir-regulon". It comprises from 5' to 3' the following genes: virR, fcrA, a relatively small emm, ennX, and a 4.6 kb version of scpA. Another common type is the "Small vir-regulon", which contains a virR deviating in its 3'-region, a relatively large emm, and a 3.5 kb version of scpA. The "Unusual vir-regulon" is less frequently detected. It closely resembles the small one, but harbors an additional 3 to 4 kb DNA fragment between emm and scpA, occasionally encoding an emm-related gene. The type of vir-regulon encoded by a GAS strain correlates to its serotype, its M class, and its expression of serum opacity factor. The structural genes of the vir-regulon are expressed at a high level during growth in exponential phase, under anaerobiosis, and at body temperature. The sensor molecule which modulates VirR activity according to these environmental conditions has not yet been detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The vir-regulon of Streptococcus pyogenes: coordinate expression of important virulence factors]. 145 95

The 9/27 and GBP mRNAs are both inducible by Interferon-gamma (IFN-gamma). The promoters of both genes contain an Interferon Stimulation Response Element (ISRE), but while the GBP gene is strongly induced transcriptionally by IFN-gamma the response of the 9/27 promoter is very weak. We investigated the molecular basis for this difference. The different IFN-gamma-responsiveness was found to have more than one reason. First, 9/27 promoter DNA was unable to bind the Gamma Interferon Activation Factor (GAF) with a single high affinity site. It efficiently competed for the association of the GAF with the GBP promoter but this competition was due to the presence of two low affinity sites, the ISRE and an ISRE-like sequence, suggesting that the GAS and ISRE, though both having clear preferences for specific proteins, may nevertheless share a certain degree of structural homology. Second, the 9/27 and GBP ISREs differed markedly in their affinities for regulatory proteins (ISGFs 1,2,3) and the GBP ISRE was more potent in mediating IFN-gamma-induced promoter activity in transient transfection. Third and most importantly, however, the strong difference between the IFN-gamma response of the two promoters was mainly due to the sequences surrounding the ISRE: the positive-acting GAS on one side and sequences with silencing properties 5' and 3' of the 9/27 ISRE on the other side. The data thus show mechanisms to both up- and down-regulate the activity of the ISRE.
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PMID:Transcriptional induction of IFN-gamma-responsive genes is modulated by DNA surrounding the interferon stimulation response element. 150 72

The promoters of two interferon-induced genes (the ISG54 and guanylate-binding protein [GBP] genes) have been analyzed in whole cells and in isolated nuclei by using a new genomic sequencing technique. The ISG54 gene contains an interferon-simulating response element (ISRE), earlier shown to be necessary and sufficient for alpha interferon (IFN-alpha) induction, that appeared complexed with proteins in both transcribing and nontranscribing cells. However, the extent of protection and hypersensitivity to DNase I or dimethyl sulfate within the ISRE region was changed upon transcriptional induction, suggesting the binding of different factors in different transcriptional states. In addition to the ISRE, the GBP gene needs a newly recognized DNA element, called the GAS, that partly overlaps the ISRE for full induction by either IFN-alpha or IFN-gamma. This GAS element was transiently protected against DNase I in the nuclei of interferon-treated cells but was not protected at later times when transcription reached maximal levels. Thus, the GAS-binding activity may be necessary only transiently for the initial assembly of a transcription initiation complex on the GBP promoter. Dimethyl sulfate methylation of genomic DNA performed on intact cells showed a characteristic sensitivity over the GAS that correlated with transcription levels and that persisted longer than did DNase I protection over the GAS. These results demonstrate the involvement of the GAS in IFN-alpha and -gamma induction of GBP and suggest the presence of an altered DNA conformation or a small protein in the major groove of the GAS associated with ongoing GBP transcription.
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PMID:Interferon induction of gene transcription analyzed by in vivo footprinting. 172 91

Evaluation of homologous regions of published M protein (emm) gene sequences from group A streptococci (GAS; Streptococcus pyogenes) was used to design three primer pairs for polymerase chain reaction (PCR) and three oligonucleotide probe sequences internal to the amplified products. One set of primers and corresponding probe should detect and lead to amplification of emm(-like) genes of virtually every type ("all M"), another ("SOR-M") should only amplify emm(-like) genes from GAS negative for serum opacity reaction (SOR) and the third ("SOR+ M") should expand only emm(-like) genes from SOR+ GAS. Using the "allM" primer pair for PCR on the genomic DNA from GAS of 29 different M types as well as from a group C and a group G streptococcal isolate, DNA fragments within the expected size range were amplified in every assay. All PCR products reacted with the "allM" probe. Related sequences were not detected in genomic DNA of an S. agalactiae and an Enterococcus faecalis isolate. Applying the "SOR-M" and "SOR+M" primers to identical assays led to mutually exclusive amplification products. The "SOR-M" and "SOR+M" probes hybridized only to their corresponding products. Exceptions to this exclusivity were the SOR- GAS of M types 3, 8, 27, 34, 42, 67, and 69, which consistently reacted only with the "SOR+M" primer/probe set. Analysis of sequence data from the amplified emm(-like) 2, 3, 18, and 19 genes revealed interesting specific features such as conserved gaps in the C-terminal sequence regions from SOR+ and the exceptional SOR- GAS strains. These data indicate the existence of a subgroup of strains among SOR- GAS and may advance our understanding of phylogenetic relationship between different serotypes of GAS.
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PMID:Application of the polymerase chain reaction to study the M protein(-like) gene family in beta-hemolytic streptococci. 178 71

Interferon (IFN)-gamma-induced expression of indoleamine 2,3-dioxygenase (IDO) gene is implicated in the antimicrobial and antiproliferative effects of IFN-gamma in cell cultures. Earlier studies identified a 96 base pair (bp) regulatory region upstream of the IDO gene that conferred IFN-gamma response to the chloroamphenicol acetyltransferase (CAT) gene linked to herpesvirus thymidine kinase promoter. The IFN-gamma-responsive region was further narrowed to a 67 bp fragment by 3' deletion. This 67 bp fragment contains several sequence elements of potential interest, including a 14 bp sequence homologous to the ISRE sequence found in IFN-alpha-inducible genes and two palindromic sequences (PE I and PE II) homologous to the GAS sequence identified in IFN-gamma-inducible genes. Site-directed mutagenesis studies showed that IFN-gamma-induced expression of IDO-CAT constructs involved cooperation between two elements: the ISRE homolog and the PE II (but not PE I). Either element alone with its flanking sequence was inadequate in conferring an IFN-gamma response to CAT reporter gene. Two IFN-gamma-regulated protein factors interacting with these two elements were identified. The factor binding to the ISRE region was induced with a slower kinetics, required new protein synthesis, and reacted with antibodies to IRF-1. The factor interacting with the PE II region appeared rapidly after treatment with IFN-gamma independently of new protein synthesis, and its binding to DNA probe was blocked by antibodies to p91 factor, reported to bind to GAS element.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of two regulatory elements in interferon-gamma-regulated expression of human indoleamine 2,3-dioxygenase gene. 755 21

Stimulation of quiescent Nb2 T cells by PRL leads to the rapid transcriptional activation of a T cell activation gene, interferon regulatory factor-1 (IRF-1). IRF-1 is induced twice by PRL in a single cell cycle, first during G1 at 30-60 min and again over early S phase at 10-12 h. By nuclear run-on transcription analysis of IRF-1 promoter-chloramphenicol acetyl transferase (CAT) constructs, the -1.7 kilobase (kb) 5'-flanking IRF-1 DNA was shown to contain elements that mediate both G1 and S phase expression. The -200 bp IRF-1 promoter DNA contains elements that respond to G1 PRL stimulation in a protein synthesis independent manner, suggesting the involvement of pre-existing factors. Further promoter deletion analysis delineated a minimal PRL responsive region between -112 and -205 bp. Within this region is a Gamma Interferon Activated Sequence or GAS, consisting of two inverted GAAA motifs (-123/-113), which confers PRL-inducible expression to a reporter gene, suggesting that GAS can function as a PRL responsive element. Further, GAS exhibits binding with nuclear proteins in a PRL-inducible, cell cycle-dependent manner. One of these proteins appears to be related to the emerging family of Signal Transducer and Activator of Transcription or Stat factors. These studies suggest that the GAS site and Stat-like proteins participate in PRL receptor signal transduction to regulate the biphasic expression of the IRF-1 gene in PRL-stimulated T cells.
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PMID:Biphasic transcriptional regulation of the interferon regulatory factor-1 gene by prolactin: involvement of gamma-interferon-activated sequence and Stat-related proteins. 765 94

The transcription factor, milk protein binding factor (MPBF/Stat5), is a member of the STAT family of signalling molecules which mediates prolactin signal transduction in lactating mammary gland by binding to GAS (gamma-interferon activation site) DNA elements. We have determined the levels of STAT factors in nuclear extracts from a variety of human breast tissues including carcinoma and normal 'resting' breast by electrophoretic mobility-shift assay. The results show that the level of STAT binding activity is low in normal 'resting' breast and benign lesions while carcinoma samples have significantly higher (P < 0.01) amounts of STAT binding activity. Supershift analysis suggests that Stat1 and possibly other members of the STAT family of signalling factors, including Stat3, are activated in breast cancer tissues.
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PMID:Elevated levels of members of the STAT family of transcription factors in breast carcinoma nuclear extracts. 771 Sep 52

Interleukin-3 (IL-3) is an important regulator of hemopoiesis and considerable effort has been directed towards the study of its mechanism of signal transduction. In this paper, we describe the first molecular identification of a STAT transcription factor that is activated by IL-3. STATs exist in a cytoplasmic, transcriptionally inactive form which, in response to extracellular signals, become tyrosine phosphorylated and translocate to the nucleus where they bind to specific DNA elements. Several of these DNA elements were found which bind proteins in an IL-3-responsive manner. Analysis of these bandshift complexes with available antibodies to the known STATs suggests that IL-3 activates the DNA-binding ability of STAT5, a protein which was originally characterized as a prolactin-responsive transcription factor in sheep. IL-5 and granulocyte-macrophage colony stimulating factor (GM-CSF), which share a common signaling receptor subunit with IL-3, also activate STAT5. Unexpectedly, two murine STAT5 homologs, 96% identical to each other at the amino acid level, were isolated and IL-3-dependent GAS binding could be reconstituted in COS cells transfected with IL-3 receptor and either STAT5 cDNA. In IL-3-dependent hemopoietic cells, both forms of STAT5 are expressed and activated in response to IL-3.
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PMID:Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. 772 Jul 7

IL-4 regulates transcription of the germ-line gamma 1 Ig gene in murine B cells and by doing so targets this isotype for switch recombination by an unknown mechanism. In this study, we have identified an IL-4-induced DNA-binding protein factor in murine B cells designated NF-IL-4-gamma 1. This factor binds specifically to a site within a 13-bp DNA sequence extending from -125 to -113 (5' CATTCACATGAAG 3') in the germ-line gamma 1 promoter and shown previously to be important for IL-4-responsive transcription. This sequence is highly homologous to the IFN-gamma activation site or GAS, and competitive binding studies demonstrate that NF-IL-4-gamma 1 can also bind to GAS elements in the promoters of two IFN-gamma-responsive genes and to an IL-4-responsive element in the germ-line epsilon Ig promoter. NF-IL-4-gamma 1 is rapidly induced in the absence of de novo protein synthesis and expression is sustained through day 4 of in vitro culture with IL-4 and LPS. Induction of NF-IL-4-gamma 1 is inhibited by the kinase inhibitor staurosporine and the factor itself requires phosphorylation for binding activity. The binding specificity and expression characteristics of NF-IL-4-gamma 1 suggest identity with other recently described IL-4-activated, GAS-binding factors that are members of the signal transducers and activators of transcription (STAT) family of cytokine-responsive transcription factors.
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PMID:IL-4 activates a latent DNA-binding factor that binds a shared IFN-gamma and IL-4 response element present in the germ-line gamma 1 Ig promoter. 772 6


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