Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modulation of gene expression by glucocorticoids involves interaction of these hormones with an intracellular receptor followed by 'transformation' of the hormone-receptor complex into a nuclear binding form. The molecular basis for the antiglucocorticoid action of high-affinity steroid analogues such as RU486 remains controversial. The effects of dexamethasone and RU486 on in vitro and in vivo properties of the receptor were compared using human lymphoblastoid IM-9 cells. In these cells, RU486 fully antagonized the glucocorticoid-specific induction of 5'-nucleotidase activity by dexamethasone. In vitro, however, RU486-bound receptor could be transformed and shown to interact specifically with cloned DNA fragments containing glucocorticoid response elements. These fragments included one from the mouse mammary tumour virus and two from the human growth hormone gene. In vivo, RU486-bound receptor did not behave like dexamethasone-bound receptor. While receptor downregulation, a property of the transformed receptor, was achieved by dexamethasone, this did not occur with RU486. Likewise, RU486 did not affect receptor half-life under conditions when this was shortened by dexamethasone. These seemingly contradictory results can be reconciled by proposing that receptor transformation by agonists involves dissociation of the receptor oligomer to reveal a DNA-binding site that pre-exists on this protein. Although cell-free receptor dissociation and therefore DNA binding can occur even when the receptor is bound to RU486, this steroid maintains receptors in the untransformed state in the intact cell and therefore behaves a glucocorticoid antagonist in vivo.
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PMID:Glucocorticoid receptors bound to the antagonist RU486 are not downregulated despite their capacity to interact in vitro with defined gene regions. 303 86

Primary hepatocytes were cultured on collagen gel in serum-free, alpha-modified Eagle's minimum essential medium containing 0.1 microM insulin, 0.1 microM dexamethasone, 10 mM pyruvate and supplements such as glucagon, epinephrine or growth hormone. The activities of alkaline phosphatase, 5'-nucleotidase and gamma-glutamyltransferase were assayed in cell extracts prepared from the cultures. All three enzyme activities were induced by glucagon, epinephrine or dibutyryl cAMP. The maximally effective concentration of glucagon was 5-10 nM for both alkaline phosphatase and 5'-nucleotidase and 100 nM for gamma-glutamyltransferase. Only alkaline phosphatase activity was suppressed by growth hormone, which caused marked suppression at about 1 microU (0.25 ng)/ml. Taurocholate also induced both alkaline phosphatase and gamma-glutamyltransferase activities at 1 mM.
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PMID:Hormonal regulations of alkaline phosphatase, 5'-nucleotidase and gamma-glutamyltransferase activities in adult rat hepatocytes cultured in serum-free medium on collagen gel. 809 10

Pneumocystis carinii pneumonia is a hallmark disease associated with AIDS. An abundant glycoprotein, termed gpA, on the surface of P. carinii is considered an important factor in host-parasite interactions. The primary structure of ferret P. carinii gpA contains a carboxyl-terminal sequence characteristic of a signal for glycosylphosphatidylinositol (GPI) anchors. Here we report the capacity for this gpA carboxyl sequence to direct attachment of a secreted protein, human growth hormone (hGH), to the membranes of COS cells. A control fusion protein (hGHDAF37) was obtained which, under the direction of the GPI signal from decay accelerating factor, directs hGH cell surface expression. A construct (phGH2-1A30) was created similar to hGHDAF37 by fusing hGH to the putative GPI signal sequence encoded in the terminal 30 residues from a ferret P. carinii gpA cDNA clone. By indirect immunofluorescent staining, hGH was detected on the surface of COS cells transfected with phGH2-1A30; this surface location was confirmed by confocal laser cytometry. Metabolic labeling with [3H]ethanolamine and subsequent immunopurification of hGH from cells transfected with phGH2-1A30 confirmed that a lipid moiety characteristic of a conventional GPI anchor was linked covalently to hGH, and cell surface hGH2-1A30 fusion protein was sensitive to enzymatic cleavage by phosphatidylinositol-phospholipase C. Furthermore, hGH2-1A30 recombinant protein cofractionated with 5'-nucleotidase, a classical GPI-anchored membrane marker. Together, these results indicate that the carboxyl-terminal residues of ferret P. carinii gpA constitute a biologically functional GPI consensus domain, thus providing a potential mechanism for antigenic variation of P. carinii gpA during P. carinii pneumonia.
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PMID:The carboxyl terminus of Pneumocystis carinii glycoprotein A encodes a functional glycosylphosphatidylinositol signal sequence. 974 3