Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Influenza A virus (IAV)-induced polymorphonuclear leukocyte (pMNL) dysfunction is important in causing secondary bacterial infections that lead to most influenza-related deaths. We previously showed that PMNLs exposed to IAV followed by a variety of stimuli (e.g., FMLP, PMA) demonstrate inhibition of various activation steps and endstage functions, suggesting IAV alters an early step in cell signalling. The present study examined IAV's effect on trimeric and monomeric G-proteins, since alterations of these proteins could explain IAV-induced PMNL dysfunction to various stimuli. PMNLs exposed to IAV for 30 min had decreased membrane-associated basal and high affinity guanosine triphosphatase (GTPase) activity compared with control cells. immunoblotting studies, using trimeric G-protein alpha and beta subunit-specific Abs, showed IAV decreased plasma membrane association of the trimeric G-proteins alpha subunits Gi2 and Gq by 33% +/- 5 and 46% +/- 8, respectively; binding of Gi3 and Gs was not altered. Similar studies involving monomeric G-proteins demonstrated that IAV decreased the membrane binding of rap1A (35% +/- 4), but not rac G-proteins. Corresponding increases in these IAV-altered G-proteins were detected in intracellular compartments. These data suggest the mechanism of IAV-induced PMNL dysfunction involves alterations in the binding of trimeric and monomeric G-proteins to plasma membranes.
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PMID:Decreased binding of specific monomeric and trimeric G-proteins with the plasma membrane of polymorphonuclear leukocytes exposed to influenza A virus. 765 Mar 87

A combination of T4 polynucleotide kinase, Escherichia coli alkaline phosphatase, yeast Saccharomyces cerevisiae capping enzyme consisting of alpha (RNA guanylyltransferase) and beta (RNA 5'-triphosphatase) subunits. and its alpha subunit without RNA 5'-phosphatase activity was used to establish a simple enzymatic method for determination of RNA species with 5'-hydroxyl, 5'-monophosphate, 5'-diphosphate or 5'-triphosphate termini. Using this method, we found that viral genome RNA (vRNA) segments of both A-type and C-type influenza viruses carry tri- or diphosphates at their 5' termini. The conclusion was based on the observations that: (i) 5' phosphorylation of vRNAs by T4 polynucleotide kinase takes place only after phosphatase treatment; and (ii) capping of vRNAs can be observed with both the intact yeast capping enzyme and its alpha subunit alone devoid of RNA 5'-triphosphatase activity; but (iii) the level of capping is higher for the alphabeta holoenzyme than the alpha subunit though the relative level varies depending on RNA preparations. The results support the de novo initiation for the RNA replication although transcription of influenza vRNAs is initiated by host cell capped RNAs as primers.
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PMID:Identification of the 5' terminal structure of influenza virus genome RNA by a newly developed enzymatic method. 972 72

The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates the recruitment of caspase-8 and cFLIPL to the MAVS signalosome and the subsequent cleavage of Ripk1 that terminates MAVS signaling. Consistently, mice with myeloid deficiency of protein geranylgeranylation showed improved survival upon influenza A virus infection. Our work revealed a critical role of protein geranylgeranylation in regulating antiviral innate immune response.
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PMID:Control of antiviral innate immune response by protein geranylgeranylation. 3114 35