Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between NS protein phosphorylation and RNA polymerase activities was determined in nucleocapsids purified from vesicular stomatitis virus grown in BHK cells. Phosphate incorporation into endogenous NS protein under transcription conditions reached a maximum value of 0.06 mol/mol of NS within 20 to 30 min, while RNA synthesis remained linear for 90 min. Phosphate incorporation into NS increased further upon addition of kinase-free NS protein but not upon addition of nucleocapsid kinase (prepared as described below), indicating that cessation of NS phosphorylation under transcribing conditions was due to substrate exhaustion. When NS was phosphorylated with 32P, less than 8% of the radiolabel was lost during subsequent transcription, indicating that this phosphate did not turn over. Treatment of nucleocapsids with 5'-p-fluorosulfonylbenzoyl adenosine resulted in greater than 90% inhibition of NS phosphorylation but had no effect on RNA polymerase activity. Fast protein liquid (Superose-6) chromatography of a nucleocapsid (L + NS) fraction resulted in complete separation of the viral (L + NS) protein from NS-phosphorylating activity. The addition of this kinase-free (L + NS) fraction to a kinase-deficient N-RNA fraction reconstituted an active RNA polymerase containing less than 20% of the original NS-phosphorylating activity. These results demonstrate that NS-phosphorylating activity is unnecessary during vesicular stomatitis virus RNA synthesis and indicate that all of the protein kinase(s) present in purified nucleocapsids is probably of cellular rather than viral origin.
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PMID:Phosphorylation of NS protein by vesicular stomatitis virus nucleocapsids: lack of effect during RNA synthesis and separation of kinase from L protein. 216 40

Phospholipid/Ca2(+)-dependent protein kinase (protein kinase C; PKC) appears to be involved in the signal-transduction pathway mediated by human leukocyte interferon (IFN) in HeLa cells. IFN treatment results in a rapid increase in [3H]phorbol 12,13-dibutyrate binding to intact cells, indicating an activation of PKC. In addition, inhibitors of PKC (H7 and staurosporine) block the induction of antiviral activity by IFN against vesicular stomatitis virus. PKC inhibitors also block the accumulation of IFN-stimulated mRNAs in the cytoplasm of HeLa cells and suppress the transcriptional induction of IFN-stimulated genes. Activation of IFN-stimulated genes is mediated through a DNA response element that is necessary and sufficient for the transcriptional response to IFN. IFN treatment induces the appearance of several DNA-binding factors that specifically recognize the response element, and the appearance of these factors is suppressed by PKC inhibitors. This observation provides evidence that PKC activity is involved during IFN-stimulated signal transduction. Although activation of PKC appears to be required for the response to IFN, agonists of PKC activity alone do not turn on expression of IFN-stimulated genes.
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PMID:Evidence for involvement of protein kinase C in the cellular response to interferon alpha. 217 63

The subcellular distribution of the regulatory (RII) subunit of cyclic AMP-dependent protein kinase (PK-A) was analyzed at the electron-microscopical level using thawed cryo-sections of Madin Darby Bovine Kidney (MDBK) cells. The highest density of labelling for RII was found on membranes of the prelysosomal compartment (PLC; marked with the cation-independent mannose 6-phosphate receptor, MPR) and the trans-Golgi network, TGN (at 20 degrees C, marked with the G protein of vesicular stomatitis virus, VSV), as well as in coated buds on the latter. Significant labelling was also localized to the cytoplasmic surface of the plasma membrane, including clathrin-coated pits and microvilli, and to early endosomes (identified using internalized HRP). In contrast, no significant label was seen over the Golgi compartments proximal to the TGN, the endoplasmic reticulum (ER) or over lysosomes. From these results we conclude that PK-A type II is associated with the membranes of precisely those subcellular compartments that are active in endocytosis and recycling of cell surface receptors. We believe these findings to be related to the well-established role of cyclic AMP in signal transduction. In particular, we propose that activation of PK-A in endocytic compartments may contribute to regulation (via phosphorylation) of the subcellular distribution of internalized surface receptors or their functional coupling to effector systems involved in signal propagation.
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PMID:Ultrastructural localization of the regulatory (RII) subunit of cyclic AMP-dependent protein kinase to subcellular compartments active in endocytosis and recycling of membrane receptors. 217 65

Antiviral effects of prostaglandins of the A series (PGAs) on Sendai, vaccinia and vesicular stomatitis viruses have previously been reported and a relationship between the antiviral actions of PGAs and interferons has been suggested. We have investigated the antiviral activity of PGAs on encephalomyocarditis (EMC) virus. Using single-cycle assays of virus replication our results indicate that PGAs only inhibit when present in the culture medium after the cells are infected, and that they are most effective during incubation periods including from 3 to 5 h post-infection. Furthermore, viral RNA synthesis is blocked in infected cells treated with PGA and, as a result, viral antigens are greatly reduced in the cytoplasm of the cells 5 h post-infection. Since the antiviral effect of PGAs is unperturbed by actinomycin D, when cellular RNA synthesis is greatly reduced, it appears unlikely that induction of new cellular proteins is the reason for the antiviral activity of PGAs. In separate experiments we were unable to demonstrate directly the induction of interferon, or of the two dsRNA-dependent enzymes, 2',5'-oligoadenylate synthetase and protein kinase, which are greatly increased in interferon-treated cells. Thus, we conclude that the antiviral activity of PGAs is unrelated to the antiviral action of interferons and involves a unique mechanism independent of cellular protein synthesis.
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PMID:Antiviral activity of prostaglandin A on encephalomyocarditis virus-infected cells: a unique effect unrelated to interferon. 241 95

Effect of (2'-5')oligoadenylate (2-5A) on cellular and viral protein and RNA syntheses was investigated with two mouse cell lines, L929 and Lz (a subclone of L929). The oligonucleotide was introduced into the cells either by using calcium phosphate coprecipitation technique or by microinjection method. In L929 cells protein and viral RNA syntheses were severely inhibited by 2-5A, whereas in Lz cells, both were only slightly inhibited. The activities of 2-5A synthetase and double-stranded (ds)RNA-dependent protein kinase were enhanced by interferon (IFN) treatment roughly to the same extent and there was no significant difference in the level of 2'-5' phosphodiesterase activity either. On the other hand, 2-5A-dependent RNase (RNase L) activity in Lz cells was low, being about 10-20% of that of L929 cells. It was increased twofold after IFN treatment, but protein synthesis of Lz cells was not as sensitive to 2-5A as that of L929 cells even after IFN treatment. L929 and Lz cells were sensitive to the antiviral effect of mouse IFN against vesicular stomatitis virus (VSV) and Mengovirus. In contrast, however, Lz cells were relatively insensitive to the antiviral effect of IFN on vaccinia virus, whereas L929 cells were sensitive.
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PMID:Comparative studies on (2'-5')oligoadenylate-related enzyme systems and the antiviral effect of interferon in two mouse cell lines which differ in (2'-5')oligoadenylate sensitivity of their protein synthesizing system. 241 28

From the NIH 3T3 clone 1 line which is normally unprotected by interferon (IFN) against lytic virus infection we have selected subclones which show high sensitivity to IFN. The selection procedure was based on encephalomyocarditis virus (EMCV) as selection agent. In the IFN-sensitive subclones thus obtained EMCV replication was inhibited by IFN to a similar degree as observed in L929 cells. Like in the original NIH 3T3 clone 1 line, however, replication of vesicular stomatitis virus (VSV) and cell multiplication were only marginally affected by IFN. We measured the levels of known IFN-induced enzymes (2-5A-synthetase, dsRNA protein kinase and 2-5A-dependent RNase) in a number of subclones and found no consistent differences to the original population. Thus, the newly acquired IFN-dependent protection against EMCV may be mediated by a different antiviral mechanism.
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PMID:Studies on interferon-sensitive cells derived from the interferon-resistant NIH 3T3 clone 1 line. 242 4

The double-stranded RNA-dependent protein kinase from human cells is a 68,000 molecular weight protein (p68 kinase), the level of which is enhanced significantly in cells treated with interferon. With a monoclonal antibody specific for p68 kinase, here we show the phosphorylation and steady-state levels of p68 kinase during virus infection. The p68 kinase is phosphorylated in interferon-treated cells during infection with encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV), and vaccinia virus, thus indicating activation of p68 kinase during these virus infections, an essential step required for autophosphorylation of p68 kinase. However, in spite of this activation, the level of p68 kinase is rapidly decreased in virus-infected cells. The half-life of p68 kinase in uninfected cells is 6 to 7 hr, whereas in EMCV-infected cells it is 2 to 3 hr. This decrease in the level of p68 kinase is dependent on the multiplicity of virus infection and it seems to be specific since other cellular proteins as well as the activity of 2'-5'-oligoadenylate synthetase are not modified. Decreased levels of p68 kinase are also observed in cells infected with VSV and vaccinia virus. In the absence of virus infection, decreased levels of p68 kinase occur in cells following incubation with poly(I).poly(C).
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PMID:Rapid decrease in the levels of the double-stranded RNA-dependent protein kinase during virus infections. 244 Jan 79

Three cell lines tera I, tera II, and PA1, derived from human teratocarcinomas were tested for their capacity to produce interferon (IFN) and for their sensitivity to both human IFN-alpha and IFN-beta. When treated with Newcastle disease virus or Sendai virus, or a synthetic polyribonucleotide, poly(rI):poly(rC), tera I cells produced no IFN and the 2',5'-oligoadenylate (2-5A) synthetase enzymatic pathway was not activated, although there was an increase in protein kinase. In contrast, tera II and PA1 cells produced IFN and both enzymatic activities were detected. IFN treatment has no effect on the growth of any of the cell lines. Tera I and PA1 cells did not develop resistance to challenge with vesicular stomatitis virus or encephalomyocarditis virus, but the growth of a type-C baboon retrovirus was inhibited. Tera II cells were protected against all three viruses. It appears that human teratocarcinoma cell lines can thus differ greatly in their ability to produce IFN and to respond to it.
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PMID:Interferon inducibility and sensitivity of human teratocarcinoma-derived cell lines. 244 Sep 57

The vesicular stomatitis virus (VSV) NS and M proteins are not only phosphorylated in vivo but are also further modified by the virion-associated protein kinase(s) concomitantly with the in vitro transcription process. Although NS phosphorylation is necessary for this transcription, no function has yet been ascribed for M protein phosphorylation. We show here that all phosphates added to M protein in vitro mapped to the trypsin-sensitive N-terminal basic domain (residues 1-43). The major site(s) (approximately 93%) corresponded to one or more of three serine residues within the first 17 amino acids. Nearly 1 mol phosphate/mol protein was added in vitro under optimal conditions suggesting that only one of these three candidate serine residues corresponds to the major site. This same M protein domain is thought to play an important role in virus RNA synthesis by inhibiting transcription. We show here that in vitro phosphorylation did not appear to affect this function. Two critical serine residues in the VSV NS protein were previously reported to be phosphorylated during in vitro transcription (D. Chattopadhyay and A. K. Banerjee, 1987, Cell 49, 407-414). The sequence flanking these NS serines is very acidic while that of all three candidate phosphoserines in the M protein is very basic. We therefore predict that at least two distinct serine-specific kinase activities are packaged in virions, one specific for M and one specific for NS.
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PMID:Phosphorylation of vesicular stomatitis virus M protein: evidence for a second virion-associated protein serine kinase activity. 253 29

The kinetics of induction of the antiviral state against two RNA viruses, vesicular stomatitis virus (VSV) and Sindbis virus, by human interferons (IFNs)-alpha, -beta, and -gamma was measured and compared with that of 2',5'-oligoadenylate (2-5A) synthetase and protein kinase in cells treated with IFNs. Both enzymes were induced in similar time courses and the induction by IFN-gamma was slower than IFN-alpha or beta. The time course of the induction of antiviral state against VSV almost paralleled with that of the enzyme induction by each IFN species. In contrast, the induction of antiviral state against Sindbis virus with IFN-gamma was as fast as that induced with IFN-alpha or beta, in spite of the slower enzyme induction by IFN-gamma. The addition of actinomycin D at the time of virus challenge did not substantially affect the induction of the antiviral state against VSV, but markedly retarded the establishment of IFN-gamma-induced antiviral state against Sindbis virus. These results suggest that the antiviral machinery against VSV is induced solely by IFN during the pretreatment, but the one against Sindbis virus involves additional cellular component(s) induced shortly after virus infection, especially in the case of IFN-gamma. Sindbis virus, but not VSV, induced a cellular double-stranded (ds) RNA-dependent protein kinase at an early stage of virus replication. The kinase appeared to phosphorylate the same protein as IFN-induced kinase in the IFN-gamma-treated and Sindbis virus-infected cells, leading to an increased phosphorylation level. These results are consistent with the idea that the Sindbis virus-induced protein kinase may be involved in the IFN-gamma-induced antiviral state against Sindbis virus.
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PMID:Possible involvement of virus-induced protein kinase in the antiviral state induced with interferon-gamma against Sindbis virus. 254 Dec 9


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