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

---

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

A role for the Epstein-Barr virus small RNA species EBER-1 in the regulation of protein synthesis has been investigated in the reticulocyte-lysate cell-free translation system. Recombinant EBER-1 was synthesized by in vitro transcription of a plasmid containing the viral gene and purified by CF11-cellulose chromatography and ribonuclease III treatment. When added to the reticulocyte lysate at 10-20 micrograms/ml or more, EBER-1 prevents the inhibition of protein synthesis caused by low concentrations of synthetic double-stranded RNA, poly(I).poly(C). This effect is eliminated by treatment of the recombinant EBER-1 with ribonuclease T1. Disruption of the secondary structure of EBER-1 by substitution of inosine for guanosine in the in-vitro-synthesized RNA impairs the ability of EBER-1 to prevent the poly(I).poly(C)-mediated inhibition of protein synthesis. These results suggest that high concentrations of EBER-1 regulate protein synthesis by blocking the activation of the double-stranded RNA-dependent eukaryotic initiation factor 2 alpha (eIF-2 alpha) protein kinase DAI (p68), and that this property is dependent on the secondary structure of the small RNA molecule.
...
PMID:Translational control by the Epstein-Barr virus small RNA EBER-1. Reversal of the double-stranded RNA-induced inhibition of protein synthesis in reticulocyte lysates. 217 60

Bacteriophage T7 expresses a serine/threonine-specific, cAMP-independent protein kinase activity encoded by the early gene 0.7. The phosphoproteins specifically resulting from gp0.7 protein kinase expression in T7-infected Escherichia coli have been examined by one-dimensional, SDS-polyacrylamide gel electrophoresis. Only seven major, stable phosphoproteins dependent on gp0.7 protein kinase expression are observed. Two of the gp0.7 protein kinase-specific phosphoproteins observed have been previously identified: the beta' subunit of RNA polymerase and the RNA processing enzyme RNase III. The gp0.7-catalyzed protein phosphorylation activity appears at 9-11 min postinfection at 30 degrees. The new phosphoproteins have a metabolic stability comparable to that of uninfected cell phosphoproteins. T7 protein kinase expression causes the phosphorylation of the same, limited set of proteins in B, C, or K strains of E. coli. Expression of the T3 and BA14 phage protein kinase activities also produces the same phosphoproteins.
...
PMID:Protein kinase of bacteriophage T7 induces the phosphorylation of only a small number of proteins in the infected cell. 218 69

RNase III activity of Escherichia coli is stimulated 4-fold after infection with bacterial virus T7. The mechanism of stimulation is based on phosphate transfer to RNase III by the T7 coded protein kinase. In vitro synthesized protein kinase also stimulates RNase III. Serine is the phosphate acceptor.
...
PMID:RNase III is positively regulated by T7 protein kinase. 640 99

Bacteriophage T7 expresses a serine/threonine-specific protein kinase activity during infection of its host, Escherichia coli. The protein kinase (gp0.7 PK), encoded by the T7 early gene 0.7, enhances phage reproduction under sub-optimal growth conditions. It was previously shown that ribosomal protein S1 and translation initiation factors IF1, IF2, and IF3 are phosphorylated in T7-infected cells, and it was suggested that phosphorylation of these proteins may serve to stimulate translation of the phage late mRNAs. Using high-resolution two-dimensional gel electrophoresis and specific immunoprecipitation, we show that elongation factor G and ribosomal protein S6 are phosphorylated following T7 infection. The gel electrophoretic data moreover indicate that elongation factor P is phosphorylated in T7-infected cells. T7 early and late mRNAs are processed by ribonuclease III, whose activity is stimulated through phosphorylation by gp0.7 PK. Specific overexpression and phosphorylation was used to locate the RNase III polypeptide in the standard two-dimensional gel pattern, and to confirm that serine is the phosphate-accepting amino acid. The two-dimensional gels show that the in vivo expression of gp0.7 PK results in the phosphorylation of over 90 proteins, which is a significantly higher number than previous estimates. The protein kinase activities of the T7-related phages T3 and BA14 produce essentially the same pattern of phosphorylated proteins as that of T7. Finally, several experimental variables are analysed which influence the production and pattern of phosphorylated proteins in both uninfected and T7-infected cells.
...
PMID:Phosphorylation of elongation factor G and ribosomal protein S6 in bacteriophage T7-infected Escherichia coli. 802 76

The E3L gene of vaccinia virus encodes the double-stranded (ds) RNA binding proteins p20 and p25 that exhibit inhibitory activity for the IFN-induced, P1/elF-2 alpha protein kinase. A region in the E3L encoded proteins (residues 156-180) shares a high degree of similarity with several proteins that bind double-helical RNA including the P1/elF-1 alpha kinase, bacterial and yeast RNase III, and a human transactivator response element/Rev response element binding protein. In this study, mutants of E3L proteins were constructed in order to determine the region of the proteins required for dsRNA binding and kinase inhibitory activity. Our data indicate that both the region necessary for dsRNA binding and for kinase inhibitory activity are located at the carboxyl terminus of the protein. The E3L proteins with 7 amino acids deleted from the carboxyl terminus (184-190) could bind to dsRNA, but with lower affinity than could the full-length protein. This protein did not detectably inhibit kinase in vitro. Deletion of 26 amino acids from the carboxyl terminus of the E3L proteins (165-190) abolished dsRNA binding activity and kinase inhibitory activity. In addition, mutations at amino acid 164, 167, or 174 severely inhibited binding to dsRNA. On the other hand, deletion of 83 amino acids from the amino terminus did not affect the proteins' ability to bind dsRNA or inhibit kinase. These results suggest that a region of sequence between amino acids 164 and 183 is necessary for E3L proteins' dsRNA binding activity. This region lies within the homologous domain that the E3L proteins share with other dsRNA binding proteins.
...
PMID:Identification of a conserved motif that is necessary for binding of the vaccinia virus E3L gene products to double-stranded RNA. 809 44

The spindle midzone, a conspicuous network of antiparallel interdigitating nonkinetochore microtubules between separating chromosomes, plays a crucial role in regulating the initiation and completion of cytokinesis. In this study, we report the use of time-lapse microscopy and a human kinesin endoribonucleases RNase III-prepared short interfering RNA (esiRNA) library to identify Kif4 as a motor protein that translocates PRC1, a spindle midzone-associated cyclin-dependent kinase substrate protein, to the plus ends of interdigitating spindle microtubules during the metaphase-to-anaphase transition. We show that Kif4 binds to PRC1 through its "stalk plus tail" domains and Kif4 and PRC1 colocalize on the spindle midzone/midbody during anaphase and cytokinesis. Suppression of Kif4 expression by Kif4 esiRNA results in the inhibition of PRC1 translocation, a block of the midzone formation, and a failure of cytokinesis. PRC1 translocation and midzone formation can be restored, and the cytokinetic defects can be rescued in Kif4 esiRNA-treated cells by coexpression of Kif4 but not its motor dead mutant Kif4md. Furthermore, we show that cyclin-dependent kinase phosphorylation of PRC1 controls the timing of PRC1 translocation by Kif4. These results, in light of the crucial role of PRC1 in midzone formation, indicate that cell cycle-dependent translocation of PRC1 by Kif4 is essential for midzone formation and cytokinesis.
...
PMID:Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis. 1562 5

The double-stranded (ds) RNA binding proteins, TRBP and PACT bind the interferon-induced protein kinase PKR and dsRNA. TRBP inhibits, whereas PACT activates PKR. They have two dsRNA binding domains (dsRBDs) and a C-terminal domain that does not bind RNA. All three domains show a strong homology between the two proteins. Interaction assays by in vitro binding, yeast two-hybrid, and immunoprecipitations show that TRBP and PACT form heterodimers in the absence of dsRNA. In cells, TRBP and PACT colocalize in specific dots of the perinuclear space. Analysis of the individual domains shows that the two dsRBDs of each protein interact with each other. In contrast, the C-terminal domain of PACT homodimerizes and interacts with its homologous region in TRBP, but the same domain in TRBP does not homodimerize. Because the C-terminal domain in TRBP binds to the tumor suppressor Merlin, the RNase III Dicer and PACT, we name it the Merlin Dicer PACT liaison (Medipal) domain. Based on known interactions Medipal is defined as aminoacids 228-366 in TRBP and 195-313 in PACT. TRBP-PACT interaction correlates with an absence of eIF2alpha activation by PACT, suggesting that the heterodimer does not activate PKR. We propose that the Medipal domain mediates specialized functions through protein-protein interactions and contributes to the RNA interference pathway and to PKR activation.
...
PMID:Interactions between the double-stranded RNA-binding proteins TRBP and PACT define the Medipal domain that mediates protein-protein interactions. 1842 Dec 56

The dsRNA binding protein (DRBP) family comprise one or more evolutionarily conserved dsRNA-binding domains (DRBD) of approximately 65-68 amino acids, are found in both eukaryotes and prokaryotes and are even encoded by plants and viruses. DRBP's do not recognize specific nucleotide sequences and primarily interact with approximately 11-16 base pairs present within A-form double helix RNAs, which can include ssRNA's with extensive secondary structure. The DRBP family include TRBP (TAR RNA binding protein), PKR (protein kinase activated by dsRNA), PACT (Protein Activator of PKR), ADAR (Adenosine deaminases acting on RNA), and the RNase III family including DICER, which collectively play important roles in mRNA elongation, RNA interference (RNAi), mRNA editing, stability, splicing and/or export and translation. Here, we focus on the role of DRBP's referred to as the NFARs (Nuclear Factors associated with dsRNA) which are translated from two major alternatively spliced products encoded from a single gene. Evidence indicates that the NFAR proteins play crucial roles in mRNA post-transcriptional regulation, including mRNA stability, export and translation and may also have an important function in host defense.
...
PMID:The NFAR's (nuclear factors associated with dsRNA): evolutionarily conserved members of the dsRNA binding protein family. 1910 22

Extract: RNA interference (RNAi), first discovered in Caenorhabdtitis elegans and now widely found and applied in a variety of organisms such as Drosophila, zebrafish and mammalian systems, has emerged to revolutionize the field of functional genomics by inducing specific and effective post-transcriptional gene silencing for loss-of-function studies. Mechanistic investigations of RNAi suggest that long double-stranded RNAs (dsRNAs) are first cleaved by the RNase III-like enzyme, Dicer, to 21-23 base pair (bp) small interfering RNAs (siRNAs). These siRNAs are resolved by ATP-dependent RNA helicase, and the resulting single-stranded RNAs are then incorporated into the RNA-induced silencing complex (RISC). The antisense strand of the siRNA duplex guides the RISC to the homologous mRNA, where the RISC-associated endoribonuclease cleaves the target mRNA, resulting in silencing of the target gene. The approach of using long dsRNA (up to 1-2 kb) in C. elegans and Drosophila to induce gene silencing cannot be similarly used in mammalian cells, where introduction of long dsRNA activates the dsRNA-dependent protein kinase PKR. PKR phosphorylates and inactivates the translation initiation factor eIF2, resulting in a non-specific gene-silencing effect. Development and implementation of the use of 21 to 23bp siRNAs, which can be prepared by chemical synthesis, in vitro transcription, or expressed in cells using siRNA expression systems, allows specific and effective gene silencing in mammalian cells to occur without activation of PKR.
...
PMID:Mammalian genome-wide loss-of-function screens using arrayed small interfering RNA expression libraries. 2070 2

RIG-I, a virus sensor that triggers innate antiviral response, is a DExD/H box RNA helicase bearing structural similarity with Dicer, an RNase III-type nuclease that mediates RNA interference. Dicer requires double-stranded RNA-binding protein partners, such as PACT, for optimal activity. Here we show that PACT physically binds to the C-terminal repression domain of RIG-I and potently stimulates RIG-I-induced type I interferon production. PACT potentiates the activation of RIG-I by poly(I:C) of intermediate length. PACT also cooperates with RIG-I to sustain the activation of antiviral defense. Depletion of PACT substantially attenuates viral induction of interferons. The activation of RIG-I by PACT does not require double-stranded RNA-dependent protein kinase or Dicer, but is mediated by a direct interaction that leads to stimulation of its ATPase activity. Our findings reveal PACT as an important component in initiating and sustaining the RIG-I-dependent antiviral response.
...
PMID:The double-stranded RNA-binding protein PACT functions as a cellular activator of RIG-I to facilitate innate antiviral response. 2150 29


1 2 Next >>

---