Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously we described human cell line 2fTGH, in which expression of guanine phosphoribosyltransferase is tightly controlled by the upstream region of interferon (IFN)-stimulated human gene 6-16. After mutagenesis of 2fTGH and selection with 6-thioguanine and IFN-alpha, we isolated 11.1, a recessive mutant that does not respond to IFN-alpha. We now describe U2, a second recessive mutant, selected similarly, that complements 11.1. U2 had no response to IFN-alpha or IFN-beta, and its response to IFN-gamma was partially defective. Although many genes did respond to IFN-gamma in U2, the 9-27 gene did not and the antiviral response of U2 cells to IFN-gamma was greatly reduced. Band shift assays showed that none of the transcription factors normally induced in 2fTGH cells by IFN-alpha (E and M) or IFN-gamma (G) were induced in U2. However, extracts of untreated U2 cells gave rise to a novel band that was increased by treatment with IFN-gamma but not IFN-alpha. Band shift complementation assays revealed that untreated and IFN-gamma-treated U2 cells lack the functional E gamma subunit of transcription factor E and that IFN-alpha-treated U2 cells do contain the functional E alpha subunit.
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PMID:Isolation and characterization of a new mutant human cell line unresponsive to alpha and beta interferons. 190 77

We have selected mutations in genes encoding components of the signaling pathway for alpha interferon (IFN-alpha) by using a specially constructed cell line. The upstream region of the IFN-regulated human gene 6-16 was fused to the Escherichia coli guanine phosphoribosyltransferase (gpt) gene and transfected into hypoxanthine-guanine phosphoribosyltransferase-negative human cells. These cells express gpt only in the presence of IFN-alpha. They grow in medium containing hypoxanthine, aminopterin, and thymidine plus IFN and are killed by 6-thioguanine plus IFN. Two different types of mutants were obtained after treating the cells with mutagens. A recessive mutant, selected in 6-thioguanine plus IFN, was completely resistant to IFN-alpha but responded normally to IFN-gamma and, unexpectedly, partially to IFN-beta. A constitutive mutant, selected in hypoxanthine-aminopterin-thymidine alone, was abnormal in expressing endogenous genes in the absence of IFN. Both types revert infrequently, allowing selection for complementation of the defects by transfection.
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PMID:Use of a selectable marker regulated by alpha interferon to obtain mutations in the signaling pathway. 251 75

A human T-T hybridoma clone with helper cell phenotype was established from fusions between a HPRT- variant of the human T-cell lymphoma Molt4, and PPD-activated normal human T-lymphocytes. The hybrid clone (MP-6) was characterized with regard to expression of markers and lymphokine secretion. The T-T hybridoma was positive for Leu 3a, and thus of T-helper cell lineage. The transferrin receptor (T-9) and the interleukin 2 (IL-2) receptor (Tac) were also expressed as judged by immunofluorescence analysis using monoclonal antibodies. The hybridoma produces B-cell stimulatory factor (BSF) with proliferation and maturation activities, growth inhibitory factor (GIF), leukocyte migration inhibitory factor (LIF) constitutively under serum free conditions, but no detectable interferons (IFN-alpha, IFN-beta, IFN-delta), nor interleukin 2 (IL-2). Weak interleukin 1 (IL-1)-like activity was found. The B-cell stimulatory factor (BSF) induced solid phase-anti-mu triggered resting B-cells obtained from human spleen, tonsil or peripheral blood to proliferate and to secrete IgM and IgG. Without anti-mu triggering the BSF had no proliferation inducing effect. The BSF was characterized and partially purified using ammonium sulphate precipitation, Blue-Sepharose, HPLC hydrophobic interaction and HPLC gel filtration chromatography. The BSF was heat labile at 56 degrees C and was present in two forms, one with high and one with intermediate hydrophobicity. The more hydrophobic form of BSF has a molecular weight of 12K-14K. Kinetic studies of the lymphokine secretion revealed that BSF was produced in detectable amounts in low density (0, 2 X 10(6) cells/ml) 18-24 h cultures. In 48 h to 72 h cultures there was a significant influence of growth inhibitory activities (GIF) produced. GIF, with an apparent MW of 90K could be absorbed out on certain tumor cell lines or on Blue-Sepharose. Further absorption analysis of BSF activities show that anti-mu triggered B-cells but neither resting B-cells nor T-cells could absorb BSF activity.
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PMID:A T-helper cell x Molt4 human hybridoma constitutively producing B-cell stimulatory and inhibitory factors. 294 47

A microarray for demonstration of a limited number of porcine cytokines was initiated. Polymerase chain reaction (PCR) products were synthesized for four house-keeping genes, cyclophilin, beta-actin, hypoxanthine phosphoribosyltransferase (HPRT) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the following cytokines: interleukin (IL)-1beta, IL-4, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, IL-18, interferon (IFN)-alpha, IFN-beta, IFN-gamma, tumour necrosis factor (TNF)-alpha, macrophage inhibition factor (MIF) and granulocyte/macrophage colony-stimulating factor (GM-CSF). Cytokine production was induced by incubation of porcine peripheral blood mononuclear cells (PBMC) with Concanavalin A (ConA) or oligodeoxynucleotide (ODN) 2216. RNA was isolated after 6 or 24 h from stimulated cells or unstimulated control cells and from intestinal biopsies. Cytokine expression was analysed using a 3-DNA Array 350(TM) labelling kit from Genisphere. Data were normalized using external control genes and analysed with the genepix pro 5.0 software. All the cytokines could be induced in PBMC and expressed on the array and the cytokines IL-6 and IFN-alpha were also analysed at protein level. All but one cytokine were expressed in samples from intestinal biopsies. Densitometric analyses of PCR products of the house-keeping genes were performed to validate the results from the microarray. Thus, this microarray will enable analyses of the cytokine profile during local and systemic infections in the pig.
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PMID:Development of a microarray for studying porcine cytokine production in blood mononuclear cells and intestinal biopsies. 1738 82