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)

The unique short (Us) segment of the genome of equine herpesvirus type 1 (EHV-1) strain KyA is comprised of six open reading frames (ORFs) that encode: a) a homolog of the Us2 protein of herpes simplex virus type 1 (HSV-1); b) a serine threonine protein kinase that is a homolog of the HSV-1 Us3 protein; c) a homolog of pseudorabies virus glycoprotein gX and HSV-2 gG; d) a novel glycoprotein, EUS4, not encoded by other herpesviruses sequenced to date; e) a homolog of HSV-1 gD; and f) a homolog of HSV-1 Us9. The KyA strain is a deletion mutant that lacks Us sequences encoding gI, gE, and a potential 10 kD polypeptide, and thus may be useful as a parent virus for the generation of live virus vaccines. To complete the elucidation of the transcriptional program of the Us segment, Northern blot hybridization and S1 nuclease analyses were performed on poly(A)(+)-selected RNA isolated from infected cells maintained under early (phosphonoacetic acid-block) and late conditions. The findings revealed that the gene (EUS2 ORF) encoding the protein kinase is expressed as an early 2.9 kb transcript that overlaps and is 3' coterminal with a 1.6 kb early transcript that encodes the gG/gX homolog (EUS3 ORF). Two transcripts of 1.6 kb and 5.8 kb are 5' coterminal and may both encode the novel glycoprotein gene EUS4. The 1.6 kb transcript terminates at a poly(A) signal site downstream of the EUS4 ORF, and the 5.8 kb transcript terminates within the inverted repeat (IR) segment. Overall, the transcriptional program of the EHV-1 KyA Us segment is complex and exhibits similarities to that of HSV-1 Us segment: a) transcripts arise from both DNA strands; b) some transcripts, including those mapping at the termini of the Us segment, extend into the IR segments and are 3' coterminal with the 1.2 kb IR6 transcript; c) at least one transcript reads through a functional polyadenylation signal; d) some transcripts encoding genes that lie in different reading frames exist as a family of overlapping mRNAs, some in an anti-sense manner. Lastly, of the six Us genes of the EHV-1 KyA strain, only those encoding the EHV-1 protein kinase and the HSV-2 gG/gX homolog are members of the early kinetic class.
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PMID:Transcriptional analyses of the unique short segment of EHV-1 strain Kentucky A. 759 4

We have compared the protein kinase activities of the R1 subunits from herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) ribonucleotide reductase following expression in Escherichia coli. Autophosphorylation activity was observed when kinase assays were performed with immunoprecipitated R1 or proteins purified to homogeneity, and the activity was stimulated by the basic protein protamine. Transphosphorylation of histones or calmodulin by purified or immunoprecipitated HSV-1 and HSV-2 R1 was not observed, and our results suggest that the activities of these two proteins are similar. We further characterized the protein kinase activity of HSV-1 R1 by producing insertion and deletion mutants constructed with a plasmid expressing R1 amino acids 1 to 449. C-terminal deletion analysis identified the catalytic core of the enzyme as comprising residues 1 to 292, and this polypeptide will be useful for structural determinations by X-ray crystallography. Insertion of a 4-amino-acid sequence at sites within the protein kinase domain identified regions essential for activity; insertions at residues 22 and 112 completely inactivated activity, and an insertion at residue 136 reduced activity sixfold. Similar insertions at residues 257, 262, 292, and 343 had no effect on activity. The ATP analog 5'-fluorosulfonylbenzoyladenosine, which covalently modifies conventional eukaryotic kinases at an essential lysine residue within the active site, did label HSV R1, but this labelling occurred outside the N-terminal domain. These data indicate that the HSV R1 kinase is novel and distinct from other eukaryotic protein kinases.
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PMID:Characterization of the novel protein kinase activity present in the R1 subunit of herpes simplex virus ribonucleotide reductase. 760 68

Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation. However, the effects of human herpes simplex virus type 1 (HSV-1) infection on cholesterol binding and internalization, intracellular metabolism, and efflux have not been evaluated. In addition, the effects of viral infection on signal transduction pathways that impact upon cholesterol metabolism have not been studied. We show in studies reported herein that HSV-1 infection of arterial smooth muscle cells enhances low density lipoprotein (LDL) binding and uptake which parallels an increase in LDL receptor steady state mRNA levels and transcription of the LDL receptor gene. HSV-2 also increases CE synthesis and 3-hydroxy- 3-methylglutaryl-CoA reductase activity but concomitantly reduces CE hydrolysis and cholesterol efflux. Interestingly, this viral infection was associated with a time-dependent decrease in protein kinase A activity and an increase in viral-induced protein kinase (VPK) activity commensurate with the accumulation of esterified cholesterol. The relationship between increased VPK activity and alterations in CE accumulation in virally infected cells was explored using an HSV-1 VPK- mutant in which the portion of the HSV-1 genome encoding VPK had been deleted. Cholesteryl ester accumulation was significantly increased (> 50-fold) in HSV-1-infected cells compared to uninfected cells. However, the HSV-1 VPK- mutant had no significant effect on CE accumulation. The relationship between VPK activity and these alterations in cholesterol metabolism was further supported by the observation that staurosporine and calphostin C (protein kinase inhibitors) reduced protein kinase activity in HSV-1-infected cells. These results suggest several potential mechanisms by which alterations in kinase activities in response to HSV-1 infection of vascular cells may alter cholesterol trafficking processes that eventually lead to CE accumulation.
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PMID:Altered cholesterol trafficking in herpesvirus-infected arterial cells. Evidence for viral protein kinase-mediated cholesterol accumulation. 764 51

The DNA sequence of 4005 nucleotides from the Kpnl O and part of Kpnl K fragments in the short unique region of infectious laryngotracheitis virus (ILTV) was determined. The sequence contained two complete and one partial open reading frames (ORFs). The partial ORF was open at the 5' end of the sequence and represented the NH2-terminal 118 amino acids (aa) of a polypeptide. Its partial predicted protein product exhibited significant homology to the US2 gene product of HSV-1 (herpes simplex virus type 1) and it homologs in other herpesviruses. ORF 2 is 471 aa long and could encode a protein of 53.8 kDa which shared aa homology with the protein kinases encoded by HSV-1 US3 and its gene homologs. Analysis of the ORF 2 aa sequence revealed domains characteristic of protein-serine/threonine (S/T) kinases of cellular and viral origin. The ORF 3 encoded a predicted protein of 601 aa (M(r) 67.5 kDa) which exhibited limited homology (18% overall identity) with the UL47 protein (major tegument protein) of HSV-1. Northern (RNA) blot hybridization and metabolic inhibitors were used to characterize the ILTV protein kinase and the 67K mRNAs. The data revealed that protein kinase is a gamma-1 gene encoding a 1.6 mRNa, while the 67K ORF is a gamma-2 gene encoding a 2 kb mRNA.
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PMID:Nucleotide sequence analysis of an infectious laryngotracheitis virus gene corresponding to the US3 of HSV-1 and a unique gene encoding a 67 kDa protein. 764 47

The 140-kDa RR1 protein from both herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) functions as the large subunit of viral ribonucleotide reductase (RR) and contains an intrinsic serine/threonine protein kinase (PK) activity at the unique NH2-terminal domain. This PK activity is capable of autophosphorylation and reported to transphosphorylate histone and calmodulin by some groups but not by others. It has been suggested that the lack of consensus in the finding of transphosphorylation activity with RR1 protein may be due to HSV strain variations used in different laboratories. In the present study, we have attempted to resolve this issue by immunospecifically isolating the 140-kDa RR1 protein from four different strains of HSV-1 including F, KOS, HF, and MP and three different strains of HSV-2 including G, 333, and MS and subjecting them to immunocomplex kinase assays. In PK assays autophosphorylation of 140-kDa RR1 was readily observed in protein immunopurified from all HSV-1 and HSV-2 strains used in this study. However, using the same assay no transphosphorylation activity was observed with either the 38-kDa RR2 protein present in immunocomplex along with the RR1, or with histone, when added as an exogenous PK substrate. This conclusion is further supported by the evidence that a commercial preparation of PK (protein kinase catalytic subunit from bovine heart) readily phosphorylated histone under the conditions used for RR1 immunocomplex kinase assay. These results show that the 140-kDa RR1 protein contains an autokinase activity but it is incapable of transphosphorylating heterologous substrates such as histone. In addition, we show that the RR enzyme complex (140 and 38-kDa proteins) is associated with purified HSV-2 virions.
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PMID:The 140-kDa RR1 protein from both HSV-1 and HSV-2 contains an intrinsic protein kinase activity capable of autophosphorylation but it is transphosphorylation defective. 788 45

The protein products of the Epstein-Barr virus (EBV) BMLF1 open reading frame have been characterized in the early productive cycle in B95-8 and Akata cells. The SM protein derived from the spliced RNA joining BSLF2 to BMLF1 is much the most abundant protein. SM is a phosphoprotein in EBV-infected cells and can be phosphorylated in vitro with casein kinase II (CKII). Computer analysis of the SM protein sequence showed a C terminal section of SM to be related to genome positional homologues of four other herpesviruses and revealed consensus CKII sites near the N termini of the EBV SM protein, the herpes simplex virus (HSV) ICP27 protein and the herpesvirus saimiri (HVS) open reading frame 57 protein. Site-directed mutagenesis of the consensus CKII site in EBV SM greatly reduced the in vitro phosphorylation of SM by CKII. The mechanism of transactivation by BMLF1 proteins has been controversial but SM was shown to transactivate gene expression from a CAT reporter construct by increasing the amount of cytoplasmic CAT mRNA. Mutagenesis of the CKII site in SM made no difference to the transactivation in this transient transfection assay.
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PMID:Epstein-Barr virus SM protein. 797 18

Superior cervical ganglion neurons from neonatal rats are dependent on nerve growth factor for their survival both in vivo and in vitro. In culture this requirement can be largely replaced by cAMP or its analogues. Since activation of protein kinase A by cAMP is likely to be the pathway by which it exerts its survival-promoting effect, we have tested the feasibility of using herpes simplex virus (HSV) as a vector for expressing survival-promoting genes in neurons by cloning the catalytic subunit of the cAMP-dependent protein kinase (PKAcat) with a metallothionein gene promoter into the HSV thymidine kinase gene by homologous recombination. About 95% of the neurons became infected using 2.5 p.f.u. per cell. When this construct was used to express PKAcat in superior cervical ganglion neurons, in the presence of nerve growth factor (NGF) increases of 1.9- to 2.4-fold in PKA activity were found 8-10 h after infection; levels remained elevated (1.4- to 2.1-fold) up to 18 h, returning to basal by 24 h. After infection in the absence of NGF, cumulative activity over 24 h was approximately 3.5-fold lower in the first 24 h. Although the level of the inhibitory regulatory subunit type I was raised by 18 h, this is unlikely to completely explain the transient activity of PKAcat. When neurons were induced to express maximum PKAcat levels in the presence of NGF and then deprived of NGF, survival was extended by up to 2 days, demonstrating a direct role for PKA in promoting survival. By this time, some neurite degeneration was beginning which appeared to be partly due to toxic effects of the virus. However, replenishment with NGF supported further survival, showing that at this time the neurons were still viable. Similar rates of survival were obtained using a tsK-based PKAcat vector, but no significant survival was obtained with parental HSV or tsK virus strains. These data demonstrate the feasibility, and highlight some of the problems, of using HSV-based vectors as tools for expressing functional survival proteins in sympathetic neurons.
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PMID:Expression of the cyclic AMP-dependent protein kinase (PKA) catalytic subunit from a herpes simplex virus vector extends the survival of rat sympathetic neurons in the absence of NGF. 798 74

An earlier report has shown that eight viral proteins with a common amino acid sequence (R/P)RA(P/S)R are nucleotidylyated in vitro by nuclear extracts from cells infected with herpes simplex virus 1. One, the product of the alpha 22 gene, is nucleotidylylated in the absence of viral proteins made late in infection. A chimeric protein (GST22P) consisting of amino acids 50-200 of the alpha 22 coding sequence fused to the C terminus of the glutathione S-transferase was nucleotidylylated by enzymes in nuclear extracts of infected or mock-infected cells and also by a casein kinase II enzyme purified from the sea star. The enzyme did not nucleotidylylate common casein kinase II substrates (casein, phosvitin) and the reaction was inhibited by heparin. The results are consistent with the hypothesis that nucleotidylylation of the eight viral proteins involves casein kinase II.
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PMID:Casein kinase II specifically nucleotidylylates in vitro the amino acid sequence of the protein encoded by the alpha 22 gene of herpes simplex virus 1. 799 47

The large subunit (R1) of herpes simplex virus (HSV) ribonucleotide reductase is a bifunctional protein consisting of a unique N-terminal protein kinase domain and a ribonucleotide reductase domain. Previous studies showed that the two functional domains are linked by a protease sensitive site. Here we provide evidence for two subdomains, of 30K and 53K, within the reductase domain. The two fragments, which were produced by limited proteolysis and were resistant to further degradation, remained tightly associated in a complex containing two molecules of each. They were capable of binding the R2 subunit of HSV ribonucleotide reductase with approximately the same affinity as the intact protein but the complex did not complement the small subunit (R2) to give an active enzyme. At low concentrations (0.4 micrograms/ml) of trypsin or V8 protease, cleavage between the subdomains was prevented by the presence of the N-terminal protein kinase domain. At higher protease concentrations (1 micrograms/ml) the N-terminal domain is extensively proteolysed and the 30K and 53K domains were generated. Identical results were obtained using purified R1 isolated from infected cell extracts or following expression in Escherichia coli. The origin of the two domains was investigated by N-terminal sequencing of the 53K fragment and by examining their reactivity with a panel of R1-specific monoclonal antibodies which we isolated and epitope mapped for that purpose. The trypsin cleavage site was found to lie between arginine 575 and asparagine 576, and proteolysis in this region was not prevented by the presence of R2 or the nonapeptide YAGAVVNDL. We propose that the ribonucleotide reductase region of HSV R1 exists in a two domain structure, and that the interdomain linking region is protected by the unique N terminus.
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PMID:Identification of structural domains within the large subunit of herpes simplex virus ribonucleotide reductase. 799 27

The nucleotide sequence of a 55098 bp region from the right end of the genome of a virulent African swine fever virus (ASFV) isolate (Malawi LIL20/1) has been determined. Translation of the sequence identified 67 major open reading frames (ORFs) which are closely spaced and read from both DNA strands. At six positions intergenic tandem repeat arrays are found. Comparison of the predicted amino acid sequences of encoded proteins with protein sequence databases identified a number of homologies. These include three subunits of RNA polymerase, a protein with homology to transcription factor SII (TFSII), a DNA ligase, two subunits of mRNA capping enzyme, a DNA topoisomerase type II, a dUTPase, a protein kinase, three helicases, a ubiquitin-conjugating enzyme, a protein with homology to the nif S and nif S-like proteins identified in some bacteria and Saccharomyces cerevisiae, a protein with homology to both a myeloid differentiation primary response antigen (MyD116) and to a herpes simplex virus-encoded neurovirulence-associated protein (ICP34.5), a protein with homology to the ASFV-encoded structural protein p22, two proteins with homology to copies of the ASFV-encoded multigene family 360 and one protein with homology to the ASFV-encoded multigene family 110. Four genes encode proteins which have homology to each other and constitute a new multigene family (MGF100). Nine ORFs encode proteins which contain predicted transmembrane domains. The possible functions of these predicted ASFV-encoded proteins are discussed and the evolutionary relationship of ASFV to other viruses are considered. Despite the similarities in genome structure and replication strategy of ASFV with poxviruses, sequence similarity between them is low and the organization of ASFV-encoded genes is not colinear with that of the orthopoxviruses.
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PMID:Nucleotide sequence of a 55 kbp region from the right end of the genome of a pathogenic African swine fever virus isolate (Malawi LIL20/1). 802 96


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