Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Influenza A2 virions were found to contain protein kinase activity which was stimulated, like in other virion-associated kinases, with Mg++ and Nonidet-P 40 but not with cyclic AMP. The kinase phosphorylated only the NP-protein fraction of the influenza virions in the in vitro reaction. In contrast, none of the influenza virion proteins were phosphorylated significantly during the process of virus production in infected chorioallantoic membranes. The in vitro and in vivo phosphorylations of influenza viral proteins were compared with those of Sendai virus (HVJ).
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PMID:Preferential phosphorylation of NP-protein of influenza A2 virus by virion-associated protein kinase. 18 30

Influenza A virus (IAV) activates the human neutrophil, but induces a dysfunctional state as well. Cell activation may contribute to the containment of the virus and/or cause local tissue damage. Certain features of the neutrophil activation response elicited by IAV are distinctive when compared with that triggered by formyl-methyl-leucyl-phenylalanine (FMLP). An atypical respiratory burst response occurs in which hydrogen peroxide, but no superoxide, is formed. This unusual respiratory burst stoichiometry persists despite marked priming of the IAV-induced response. A comprehensive examination of the activation cascade initiated by these stimuli failed to show an explanation for these differences. Both IAV and FMLP comparably stimulate inositol trisphosphate and phosphatidic acid production. The subsequent increase in intracellular calcium (Ca2+i) upon FMLP stimulation was more dependent on extracellular Ca2+ than with IAV activation, but both stimuli induced Ca2+ influx. FMLP and IAV exhibited equal susceptibility to inhibition by protein kinase inhibitors in eliciting the respiratory burst, and actin polymerization occurred in response to each agonist. A possible explanation for the anomalous respiratory burst induced by IAV is that O2- is generated at an intracellular site inaccessible to assay, and/or virus binding to sialic acid constituents of the plasma membrane alters the O2- generating capacity of the respiratory burst oxidase; evidence for each mechanism is offered.
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PMID:Comparison of influenza A virus and formyl-methionyl-leucyl-phenylalanine activation of the human neutrophil. 131 Jun 28

The P68 protein kinase is a serine/threonine kinase induced by interferon treatment and activated by double-stranded RNAs (dsRNAs). Once activated, the kinase phosphorylates its natural substrate, the alpha subunit of eukaryotic initiation factor 2 (eIF-2) leading to potential limitations in functional eIF-2 and decreases in protein synthesis initiation. We have recently purified from influenza virus-infected cells a P68 kinase inhibitor, found to be a 58-kDa cellular protein. We have now investigated the mechanisms by which the 58-kDa inhibitor regulates P68 kinase activity and how the inhibitor itself is controlled. The 58-kDa inhibitor did not function by degrading or sequestering the dsRNA activator of P68 but could repress phosphorylation of eIF-2 alpha by an already activated protein kinase. Utilizing antibody prepared against a 58-kDa-specific peptide, we showed that the 58-kDa proteins from infected and uninfected cells were present in equivalent amounts. Although kinase inhibitory activity could not be detected in crude uninfected cell extracts, ammonium sulfate treatment unmasked this activity and allowed purification of the cellular inhibitor with identical chromatographic properties as that from influenza virus-infected cells. Finally, we have identified and partially purified a specific inhibitor of the 58-kDa protein which we refer to as an "anti-inhibitor." Based on these data, we present a model depicting the complex regulation of the interferon-induced protein kinase in eukaryotic cells.
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PMID:Characterization and regulation of the 58,000-dalton cellular inhibitor of the interferon-induced, dsRNA-activated protein kinase. 137 38

The protein kinase activity associated with purified influenza virus has been examined. By use of a radiolabelled photoreactive ATP analogue (3'-O-(4-benzoyl) benzoyl adenosine triphosphate) a 47 kD polypeptide has been identified that binds ATP. A comparison of the sensitivity of the kinase activity and the 47 kDa polypeptide labelling to inhibitors indicate that the 47 kDa polypeptide is likely to represent the major protein kinase activity of the virus. The virus associated protein kinase phosphorylates the synthetic peptide RREEETEEE, a peptide substrate for casein kinase II. Antiserum directed against casein kinase II revealed a positive signal in immunoblots of purified virus. We propose that the major protein kinase activity associated with purified virus preparations is host cell casein kinase II.
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PMID:Characterisation of the influenza virus associated protein kinase and its resemblance to casein kinase II. 164 7

A number of eukaryotic viruses have evolved mechanisms to downregulate activity of the interferon-induced, double-stranded RNA-activated protein kinase (referred to as P68 based on its Mr of 68,000 in human cells). This control is essential because once activated, the P68 kinase phosphorylates its natural substrate, the alpha subunit of the eukaryotic protein synthesis initiation factor 2 (eIF-2), limiting functional eukaryotic protein synthesis initiation factor 2 available for protein synthesis initiation. We have previously shown that influenza virus encoded a specific mechanism to repress the autophosphorylation and activity of P68. Using in vitro assays for P68 inhibition, we now have purified, to near homogeneity, the P68 repressor from influenza virus-infected cells. The purified product inhibited both the autophosphorylation of P68 as well as phosphorylation of the alpha subunit of eukaryotic protein synthesis initiation factor 2 by the kinase. We tested for both protease and phosphatase activity but found neither activity associated with the purified inhibitor. Surprisingly we found the purified repressor, which had an apparent Mr of approximately 58,000, was a cellular and not a viral-encoded protein. Possible mechanisms by which influenza virus activates this cellular regulator of the protein kinase, thereby minimizing potential antiviral effects of interferon, are discussed.
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PMID:Purification and partial characterization of a cellular inhibitor of the interferon-induced protein kinase of Mr 68,000 from influenza virus-infected cells. 169 20

All proteins of this world are constructed in compliance with the same rule. Accordingly, two totally unrelated proteins, on the average, share 30 identical tripeptides, two tetrapeptides, and one pentapeptide per 500 residues. With this in mind, the 221-residue-long influenza virus hemagglutinin II (IVHA-II), as a representative of alien antigens, was compared with three diverse proteins representing the host: 533-residue-long chicken c-src protein kinase (c-src product of the cellular oncogene of Rous sarcoma virus), 595-residue-long human estrogen receptor, and 585-residue-long human serum albumin. Forty-three tripeptides, two tetrapeptides, and one pentapeptide of IVHA-II were also found in one or the other of the three host proteins. Six regions of IVHA-II (9-22 residues long) in which oligopeptides were clustered that were identical to their host oligopeptides were defined as "host-homologous" regions, and the remaining regions were called "nonself" or "pathogen-specific" regions. Because the total number of host proteins is vastly more than three, host-homologous regions were no doubt underestimated, while only one or two regions of IVHA-II must remain as truly pathogen-specific. Nevertheless, oligopeptide analysis of two known T-cell response-eliciting peptide fragments and one known inert peptide fragment of a virus and a malarial protozoan readily revealed the latter to be a host-homologous region. Of the two known T-cell response-eliciting peptide fragments, one was more nonself than the other. Not surprisingly, the more nonself fragment elicited helper T-cell response from individuals of diverse major histocompatibility complex haplotypes, whereas the less nonself fragment elicited cytotoxic T-cell response only from HLA-A2 human individuals.
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PMID:Many peptide fragments of alien antigens are homologous with host proteins, thus canalizing T-cell responses. 170 30

Considerable progress has been made in the understanding of the molecular biology of the human interferon system. The genes encoding the interferons, their receptors, and the proteins that mediate many of their biological effects have been molecularly cloned and characterized. The availability of complete cDNA clones of components of the interferon systems has contributed significantly to our understanding of both the biology and the biochemistry of the antiviral actions of interferons. At the biological level, the antiviral effects of interferon may be viewed to be virus-type nonspecific. That is, treatment of cells with one type or even subspecies of interferon often leads to the generation of an antiviral state effective against a wide array of different RNA and DNA animal viruses. However, at the biochemical level, the antiviral action of interferon is often virus-type selective. That is, the apparent molecular mechanism which is primarily responsible for the inhibition of virus replication may differ considerably between virus types, and even host cells. For example, the IFN-regulated Mx protein selectively inhibits influenza virus but not other viruses when constitutively expressed in mouse cells. The IFN-regulated 2',5'-oligoadenylate synthetase selectively inhibits EMC and mengo viruses, two picornaviruses, but not viruses of other families when constitutively expressed in transfected cells. Some viruses are typically insensitive to the antiviral effects of interferon, both in cell culture and in intact animals. This lack of sensitivity to IFN may result from a virus-mediated direct antagonism of the interferon system. For example, in the case of adenovirus, the activation of the IFN-regulated RNA-dependent P1/elF-2 protein kinase is blocked by the virus-associated VA RNA. The relative sensitivity to interferon of different animal viruses varies appreciably. All three of the basic components required to measure an antiviral response may play a role in determining the relative effectiveness of the antiviral response: the species of interferon administered; the kind of cell treated; and, the type of virus used to challenge the interferon-treated host cell. Thus, the relative sensitivity to interferon observed for a particular interferon-cell-virus combination is likely the result of the equilibrium between the many agonists and antagonists which contribute to the overall response. That is, the relative sensitivity of a virus to the inhibitory action of IFN is governed by the qualitative nature and quantitative amount of the individual IFN-regulated cell proteins that may collectively contribute to the inhibition of virus replication.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antiviral actions of interferon. Interferon-regulated cellular proteins and their surprisingly selective antiviral activities. 171 Dec 53

To study the mechanisms by which the influenza A virus RNA-dependent RNA polymerase switches from transcription to replication we have devised a riboprobe protection technique with which we analyzed the 3' end sequence of (+)-strand RNA products of an in vitro transcription reaction containing purified virion-RNP complexes in the presence and the absence of the putative regulatory proteins NP and NS1. We found that the addition of these proteins did not result in the synthesis of full-length (+)-strand RNA products resulting from read-through of the polyadenylation signal or replication. Because NS1 and NP are both phosphoproteins we searched for protein kinase activity that might play a role in regulating RNA synthesis. We showed that virion RNP complexes phosphorylated NS1 but possessed no autophosphorylating activity. Soluble NP protein derived from RNP complexes did not phosphorylate NS1, but did phosphorylate casein. When NP protein was dephosphorylated, however, it no longer phosphorylated casein. We also showed that NS1 was an ssRNA-binding protein which binds nonspecifically to all ssRNA, and that this activity is not dependent on its state of phosphorylation.
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PMID:Influenza A virus in vitro transcription: roles of NS1 and NP proteins in regulating RNA synthesis. 182 5

The surface glycoproteins of influenza A viruses are the viral components first recognized by the immune system of the infected host, and they are the viral proteins first to contact the infecting cell. Cleavage of the hemagglutinin (HA) is the presupposition for the uptake and fusion between viral and endosomal membranes at a relatively low pH. If this cleavage does not occur during synthesis and migration within the cell, an external trypsin-like protease has to activate the virus with a non-cleaved HA. This latter property is presumably the reason, why such a large reservoir of non-pathogenic influenza A viruses could be built up in water fowl. Especially feral ducks can disseminate influenza viruses along their flight routes all over the world. The role of the neuraminidase (NA) in the infectious process is not so clear. Its main task in the natural infection seems to be removal of mucoids at the site of entry and in this way to start the primary infection. The synthesis of the viral proteins is a highly regulated process. There is not only a transcriptional but also a translational control. The viral glycoproteins belong to the late proteins. Specifically their synthesis can be inhibited by compounds acting in completely different ways like a specific methylase inhibitor (3DA-Ado), a protein phosphokinase C inhibitor (H7), or a lipid solvent (DMSO). It remains to be determined whether the underlining mechanism is in all these cases the same, namely posttranscriptional modification of viral mRNA. All these viral components do not act separately but they cooperate in their functions and sometimes interfere with each other.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis and function of influenza A virus glycoproteins. 193 Jan 3

Influenza virus type A has been shown to establish a translational control system such that during infection there is a dramatic inhibition of host cell protein synthesis and viral mRNAs are selectively and efficiently translated. The following review summarizes the complex strategies employed by influenza to accomplish these goals. These include: (i) preventing newly made cellular mRNAs from entering the cytoplasm of infected cells; (ii) inhibiting the initiation and elongation steps of translation of preexisting cellular mRNAs; (iii) possessing RNAs with structural features which enhance translation; (iv) encoding mechanisms to downregulate the interferon induced protein kinase thus allowing overall protein synthesis levels to remain high.
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PMID:Translational control in influenza virus-infected cells. 213 54


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