Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.68810313
Competition experiments demonstrate that the carboxyl terminal region of PKR , to which pE 3 binds , overlaps the region with which eIF2alpha and the pseudosubstrate pK 3 interact , suggesting that pE 3 may also prevent PKR activation by masking the substrate binding domain . 0.68810313^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.94791137
Thus , PKR responds as trans acting factor to the 2 APRE . 2 APRE RNA forms a stable , 17 bp stem loop structure and strongly activates PKR in vitro , inducing eIF2alpha phosphorylation . 0.94791137^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.56439063
Here we report that PKR is highly activated following infection with alphaviruses Sindbis ( SV ) and Semliki Forest virus ( SFV ) , leading to the almost complete phosphorylation of eIF2alpha . 0.56439063^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The Mr 68 , 000 phosphoprotein is structurally identical to the interferon induced , double stranded RNA activated protein kinase ( P 1 ) which phosphorylates the alpha subunit of eucaryotic initiation factor 2 ( eIF 2 ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
This control is essential because once activated , the P 68 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 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
When activated by low concentrations of dsRNA , the p 68 kinase becomes phosphorylated and thereby catalyzes the phosphorylation of the protein synthesis initiation factor , eIF 2 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The phosphorylated p 68 kinase then can catalyze the phosphorylation of exogenous substrates , such as eIF 2 and histone . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Association of a M ( r ) 90 , 000 phosphoprotein with protein kinase PKR in cells exhibiting enhanced phosphorylation of translation initiation factor eIF 2 alpha and premature shutoff of protein synthesis after infection with gamma 134 . 5 mutants of herpes simplex virus 1 . ^^^ Analyses of the posttranslational modifications of translation initiation factor eIF 2 showed the following : ( 1 ) eIF 2 alpha was selectively phosphorylated by a kinase present in ribosome enriched fraction of cells infected with gamma 134 . 5 virus . ( 2 ) Endogenous eIF 2 alpha was totally phosphorylated in cells infected with gamma 134 . 5 virus or a virus lacking the 3 ' coding domain of the gamma 134 . 5 gene but was not phosphorylated in mock infected or wild type virus infected cells . ( 3 ) Immune precipitates of the PKR kinase that is responsible for regulation of protein synthesis of some cells by phosphorylation of eIF 2 alpha yielded several phosphorylated polypeptides . ^^^ We conclude that in the absence of gamma 134 . 5 protein , PKR kinase complexes with the p 90 phosphoprotein and shuts off protein synthesis by phosphorylation of the alpha subunit of translation initiation factor eIF 2 . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
As a result of activation , PKR becomes autophosphorylated and catalyzes phosphorylation of the alpha subunit of protein synthesis eukaryotic initiation factor 2 ( eIF 2 ) . ^^^ P 58 , expressed as a histidine fusion protein in Escherichia coli , blocked both the autophosphorylation of PKR and phosphorylation of the alpha subunit of eIF 2 . ^^^ Computer analysis revealed that P 58 contains regions of homology to the DnaJ family of proteins and a much lesser degree of similarity to the PKR natural substrate , eIF 2 alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Activation of PKR by double stranded RNAs leads to the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) and a resultant block to protein synthesis initiation . ^^^ Finally , murine PKR activity and endogenous levels of eIF 2 alpha phosphorylation were reduced in the p 58 expressing cell lines compared with control cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
TRBP inhibited phosphorylation of the interferon induced ribosome associated protein kinase PKR and of the eukaryotic translation initiation factor eIF 2 alpha in a transient expression system in which the translation of a reporter gene was inhibited by the localized activation of PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We have investigated whether the La antigen can regulate the activity of PKR and have observed that both the autophosphorylation of the protein kinase that accompanies its activation by dsRNA and the dsRNA dependent phosphorylation of the alpha subunit of polypeptide chain initiation factor eIF 2 by PKR are inhibited in the presence of recombinant La antigen . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In a murine interleukin 3 ( IL 3 ) dependent cell line , IL 3 deprivation resulted in increased autophosphorylation of double stranded RNA dependent protein kinase ( PKR ) that has been reported to inhibit protein synthesis by phosphorylating the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) . ^^^ In vitro kinase studies comparing the autophosphorylated 64 kDa PKR with the nonphosphorylated 60 kDa PKR confirmed that only the 64 kDa form was active for eIF 2 alpha phosphorylation . ^^^ PKR activation in vivo was associated with phosphorylation of eIF 2 alpha and inhibition of protein synthesis . ^^^ Addition of IL 3 to deprived cells elicited a reciprocal response characterized by the rapid dephosphorylation of PKR and eIF 2 alpha , indicating inactivation of PKR . ^^^ Furthermore , upon IL 3 addition , a 97 kDa phosphotyrosine containing protein becomes rapidly and transiently associated with PKR prior to dephosphorylation of PKR and eIF 2 alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Activated PKR inhibits protein synthesis by phosphorylating initiation factor eIF 2 alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Further , levels of endogenous eIF 2 alpha phosphorylation in RBD 1 minus cell lines were reduced , suggesting that such mutants act in a dominant negative manner to inhibit the function of endogenous PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Incubation of HUVE cells with the synthetic dsRNA , poly ( 1 ) . poly ( C ) , activates PKR with increased autophosphorylation , increased phosphorylation of the translation factor eIF 2 alpha , and increased activation of the transcription factor NF kappa B . ^^^ NF kappa B is also activated by IL 1 beta in HUVE cells , but this activation occurs without increased PKR autophosphorylation or eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Levels of endogenous eIF 2 alpha phosphorylation were significantly more diminished in PKR M 7 overexpressing cells compared with PKR M 1 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
To elucidate whether protein synthesis inhibition requires eIF 2 alpha phosphorylation and whether eIF 2 alpha phosphorylation is mediated by the double stranded RNA dependent protein kinase ( PKR ) , we studied protein synthesis in response to calcium depletion mediated by calcium ionophore A 23187 in cell lines overexpressing wild type eIF 2 alpha , a mutant eIF 2 alpha ( S51A ) that is resistant to phosphorylation , or a dominant negative mutant PKR ( K296P in catalytic subdomain 2 ) . ^^^ Expression of either mutant eIF 2 alpha or mutant PKR partially protected NIH3T3 cells from inhibition of protein synthesis upon A 23187 treatment . ^^^ In a COS 1 monkey cell transient transfection system , increased eIF 2 alpha phosphorylation in response to A 23187 treatment was inhibited by expression of the dominant negative PKR mutant . ^^^ Overexpression of the PKR regulatory RNA binding domain , independent of the PKR catalytic domain , was sufficient to inhibit increased phosphorylation of eIF 2 alpha upon A 23187 treatment . ^^^ Taken together , our data show that calcium depletion activates PKR to phosphorylate eIF 2 alpha , and this activation is likely mediated through the PKR RNA binding domain . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The double stranded RNA ( dsRNA ) activated protein kinase , now called PKR , was first discovered by virtue of its ability to phosphorylate translation initiation factor eIF 2 and inhibit its activity . ^^^ It seems likely that , in addition to eIF 2 , PKR has other substrates including the protein 1 kappa B , which regulates the transcription of certain genes . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR phosphorylates translation initiation factor eIF 2 alpha on Ser 51 , resulting in inhibition of protein synthesis and cell growth arrest . ^^^ Consequently , it is possible that cell transformation by dominant negative PKR mutants is caused by inhibition of eIF 2 alpha phosphorylation . ^^^ Here , we demonstrate that in NIH 3T3 cells transformed by the dominant negative PKR mutant ( PKR delta 6 ) , eIF 2 alpha phosphorylation is dramatically reduced . ^^^ These results are consistent with a critical role of phosphorylation of eIF 2 alpha in control of cell proliferation , and indicate that dominant negative PKR mutants transform cells by inhibition of eIF 2 alpha phosphorylation . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
At present , there are two distinct mammalian eIF 2 alpha kinases that have been cloned , the double stranded RNA dependent eIF 2 alpha kinase ( PKR ) and the heme regulated eIF 2 alpha kinase ( HRI ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Upon activation , PKR phosphorylates and thereby inactivates the protein synthesis initiation factor eIF 2 , resulting in the cessation of protein synthesis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Two mammalian eIF 2 kinases , the double stranded RNA dependent kinase ( PKR ) and heme regulated inhibitor kinase ( HRI ) , have been characterized by sequencing , revealing shared sequence and structural features distinct from other eukaryotic protein kinases . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The autophosphorylation of interferon ( IFN ) induced double stranded RNA dependent p 68 protein kinase ( PKR ) and phosphorylation of the alpha subunit of the translation initiation factor eIF 2 were inhibited by 10 mM 2 aminopurine in vitro . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The gene for the RNA dependent eIF 2 alpha protein kinase ( PKR ) was isolated from mouse genomic DNA and characterized . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The effects of the two vaccinia virus gene products were compared in an in vivo system in which translation of a reporter gene ( dihydrofolate reductase or eukaryotic translation initiation factor 2 alpha [ eIF 2 alpha ] ) was inhibited because of the localized activation of PKR . ^^^ We propose that the K3L inhibitor acts through its homology to eIF 2 alpha to interfere with the interaction of eIF 2 alpha with PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Purified recombinant K3L gene product , pK3r , has potent effects on activation of double stranded ( ds ) RNA dependent , initiation factor 2 alpha ( eIF 2 alpha ) specific protein kinase ( PKR ) in in vitro reactions . ^^^ In addition , pK3r reduces the autophosphorylation of immunopurified PKR , as well as its ability to phosphorylate the alpha subunit of purified eIF 2 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We have investigated this possibility using the rabbit reticulocyte cell free translation system in which protein synthesis is inhibited by dsRNA due to activation of PKR and phosphorylation of initiation factor eIF 2 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The P 58 protein inhibits both the autophosphorylation of PKR and the phosphorylation of the PKR natural substrate , the alpha subunit of eukaryotic initiation factor eIF 2 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
A peptide of 65 68 kDa , which was phosphorylated concurrently with eIF 2 alpha in extracts of pretreated cells , was identified as the interferon inducible , double stranded RNA ( dsRNA ) regulated protein kinase ( PKR ) . ^^^ When incubated with reovirus dsRNA , extracts derived from cells with depleted ER Ca2+ stores displayed greater degrees of phosphorylation of PKR and of eIF 2 alpha than did control extracts . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Endogenous inhibitors of the dsRNA dependent eIF 2 alpha protein kinase PKR in normal and ras transformed cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
This reduction began after 3 h of interferon treatment and was correlated with the appearance of phosphorylated double stranded RNA dependent eIF 2 alpha kinase ( PKR ) measured in vitro . ^^^ The autocrine effect of IFN resulted in elevated PKR activity , increased phosphorylation of eIF 2 alpha , and diminished eIF 2B activity . ^^^ These results suggest that interferon regulates the initiation of protein synthesis by a mechanism involving PKR , eIF 2 alpha phosphorylation , and eIF 2B activity . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We show that plant eIF 2alpha ( peIF 2alpha ) and mammalian eIF 2alpha ( meIF 2alpha ) are phosphorylated similarly by both the double stranded RNA binding kinase , pPKR , present in plant ribosome salt wash fractions and the meIF 2alpha kinase , PKR . ^^^ In addition , the inhibition of brome mosaic virus RNA in vitro translation in wheat germ lysates by the addition of double stranded RNA , phosphorylated peIF 2alpha , meIF 2alpha , or activated human PKR suggests that plant protein synthesis may be regulated via phosphorylation of eIF 2alpha . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The initial step of protein synthesis is regulated by the eukaryotic initiation factor 2 ( eIF 2 ) whose phosphorylation in the alpha subunit by specific kinases , as double stranded RNA dependent protein kinase ( PKR ) , produces an inhibition of the translational rates . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
When incubated with double stranded RNA , extracts derived from arsenite treated cells displayed greater degrees of phosphorylation of PKR and eIF 2alpha than did control extracts . ^^^ Cells overexpressing a dominant negative PKR mutation resisted translational inhibition and eIF 2alpha phosphorylation in response to ER or cytoplasmic stressors . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Protein synthesis ceases at late times post infection and the translation initiation factor eIF2alpha is phosphorylated by the cellular PKR kinase [ Chou et al . ( 1990 ) Science , 252 , 1262 1266 ; ( 1995 ) Proc . ^^^ Since this inhibition involves the accumulation of phosphorylated eIF2alpha , the element identified by the suppressor mutations may be a discrete PKR activator . ^^^ Instead , the virus deliberately activates PKR and encodes a separate function which selectively prevents the phosphorylation of at least one PKR target , eIF2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
There are two mammalian eIF 2alpha kinases : the double stranded RNA dependent kinase ( PKR ) and heme regulated inhibitor kinase ( HRI ) , and the yeast GCN 2 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Furthermore , the isolated kinase domain ( residues 228 551 ) undergoes autophosphorylation and sequentially transphosphorylates both mutant K296P PKR and wild type eIF 2alpha in vitro . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In human cells infected with herpes simplex virus 1 the double stranded RNA dependent protein kinase ( PKR ) is activated but phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 ) and total shutoff of protein synthesis is observed only in cells infected with gamma ( 1 ) z34 . 5 mutants . ^^^ These results indicate that in infected cells , gamma ( 1 ) 34 . 5 interacts with and redirects phosphatase to dephosphorylate eIF 2alpha to enable continued protein synthesis despite the presence of activated PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR phosphorylates initiation factor eIF2alpha , thereby inhibiting protein synthesis , and also activates the transcription factor , nuclear factor kappaB ( NF kappaB ) , by phosphorylating the inhibitor of NF kappaB , IkappaB . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Activated PKR in turn phosphorylated its natural substrate , the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 ) , thereby inhibiting initiation of host cell translation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Since the PKR activation state and therefore the eIF 2 alpha phosphorylation state change with cell density and nutritional status , we routinely set up consistent feeding schedules and recommend the collection of data over a range of cell densities . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Protein kinase PKR is activated in mammalian cells during viral infection , leading to phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2alpha ) and inhibition of protein synthesis . ^^^ Recent studies have observed that expression of mammalian PKR in yeast leads to a slow growth phenotype due to hyperphosphorylation of eIF 2alpha . ^^^ In this report , we observed that while DRBD sequences are required for PKR to function in the yeast model system , these sequences are not required for in vitro phosphorylation of eIF 2alpha . ^^^ Targeting to ribosomes may enhance in vivo phosphorylation of eIF 2alpha , by providing PKR access to its substrate . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The mammalian double stranded RNA activated protein kinase PKR is a component of the cellular antiviral defense mechanism and phosphorylates Ser 51 on the alpha subunit of the translation factor eIF 2 to inhibit protein synthesis . ^^^ Regulation of the protein kinase PKR by the vaccinia virus pseudosubstrate inhibitor K3L is dependent on residues conserved between the K3L protein and the PKR substrate eIF2alpha . ^^^ High level expression of PKR is lethal in the yeast Saccharomyces cerevisiae because PKR phosphorylates eIF2alpha and inhibits protein synthesis . ^^^ Truncation of , or point mutations within , the C terminal portion of the K3L protein , homologous to residues 79 to 83 in eIF2alpha , abolished PKR inhibitory activity , whereas the hyperactivating mutation , K3L H47R , increased the homology between the K3L protein and eIF2alpha adjacent to the phosphorylation site at Ser 51 . ^^^ Biochemical and yeast two hybrid analyses revealed that the suppressor phenotype of the K3L mutations correlated with the affinity of the K3L protein for PKR and was inversely related to the level of eIF2alpha phosphorylation in the cell . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Earlier studies have shown that infection of human cells by herpes simplex virus 1 ( HSV 1 ) results in the activation of RNA dependent protein kinase ( PKR ) but that the alpha subunit of eIF 2 is not phosphorylated and that protein synthesis is unaffected . ^^^ We conclude that the mechanism by which Sup 1 blocks the shutoff of protein synthesis associated with phosphorylation of eIF 2alpha by the activated PKR is not readily explainable by a secondary mutation characterized by a deletion . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The PKR phosphorylate eIF 2 alpha that leads to blocking of protein synthesis , mediates signal transduction via NF kappa B and / or probably IRF 1 , and is also involved in apoptosis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
These results support , but do not directly prove , contentions that HSV ICP 34 . 5 interacts with the PKR pathway to restore translation in non permissive cells , and that SV 40 large T antigen has a similar functional role , but acts downstream of the site of ICP 34 . 5 interaction ( eIF2alpha ) in the pathway . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Homologous regions of the alpha subunit of eukaryotic translational initiation factor 2 ( eIF2alpha ) and the vaccinia virus K3L gene product interact with the same domain within the dsRNA activated protein kinase ( PKR ) . ^^^ The vaccinia virus K3L gene product , pK 3 , binds to the dsRNA activated protein kinase , PKR , reducing its ability to interact with and phosphorylate eIF2alpha . ^^^ On the basis of this characteristic and the homology of pK 3 to the N terminus of eIF2alpha , several laboratories have utilized pK 3 to investigate the molecular determinants that specify substrate recognition by PKR . ^^^ The data presented here demonstrate that the natural substrate , eIF2alpha , also binds to PKR in vitro and interacts with the same or an overlapping domain within PKR . ^^^ A truncated form of eIF2alpha , representing the N terminal 123 amino acids and containing the regions of homology to pK 3 , retains the ability to bind PKR . pK 3 , eIF2alpha , and the truncated form of eIF2alpha all bind to the C terminus of PKR containing the catalytic domain , but not to the regulatory N terminus . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
TNF alpha induced apoptosis correlated with increased phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 alpha ) , the primary physiological substrate of the PKR . ^^^ Taken together , these studies identify a novel requirement for PKR in stress induced apoptosis that is mediated through eIF 2 alpha phosphorylation . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
P58IPK functions to represses PKR mediated phosphorylation of the eukaryotic initiation factor 2alpha subunit ( eIF 2alpha ) through a direct interaction , thereby relieving the PKR imposed block on mRNA translation and cell growth . ^^^ When coexpressed with PKR in yeast , P58IPK repressed PKR mediated eIF 2alpha phosphorylation , inhibiting the normally toxic and growth suppressive effects associated with PKR function . ^^^ Conversely , introduction of P52rIPK into these strains resulted in restoration of both PKR activity and eIF 2alpha phosphorylation , concomitant with growth suppression due to inhibition of P58IPK function . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In the present study , the effect of agents that increase intracellular calcium levels by different mechanisms , as well as repercussion on the rate of protein synthesis , including phosphorylation of initiation factor 2alpha subunit , and double stranded RNA dependent eIF 2alpha kinase ( PKR ) activity were analyzed . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR has been shown to play a variety of important roles in the regulation of translation , transcription , and signal transduction pathways through its ability to phosphorylate protein synthesis initiation factor eIF 2 , 1 kappaB ( the inhibitor of NF kappaB ) , and other substrates . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The interferon induced , double stranded RNA ( dsRNA ) activated protein kinase , PKR , inhibits protein synthesis via phosphorylation of the alpha subunit of the translation initiation factor eIF 2 . ^^^ A kinase insert region N terminal of PKR kinase subdomain 5 , which is conserved among eIF2alpha kinases , has been proposed to determine substrate specificity of these kinases . ^^^ To investigate the function of this kinase insert region , selective PKR mutants were generated , and kinase activities and eIF2alpha affinities were analyzed in vitro . ^^^ The deletion of the conserved sequence ( amino acids 362 370 ) resulted in a protein that had no kinase activity and only about 25 % of wild type eIF2alpha binding , suggesting that this sequence is not only required for PKR kinase activity but also is important for substrate interaction . ^^^ It was determined that the hydrophobicity of the conserved sequence of PKR is required for kinase activity but is not crucial for eIF2alpha binding . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In addition , selected RNAs are able to activate or repress wild type PKR autophosphorylation as well as its phosphorylation of protein synthesis initiation factor eIF 2 , suggesting full length PKR can bind to and be regulated by RNAs containing a tandem A G mismatch . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In particular , clotrimazole causes a sustained depletion of intracellular Ca2+ stores , which results in activation of PKR , phosphorylation of eIF2alpha , and thereby in inhibition of protein synthesis at the level of translation initiation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
These mutations also impaired autophosphorylation and eukaryotic initiation factor 2 subunit alpha ( eIF2alpha ) phosphorylation by PKR in vitro . ^^^ We found that the yeast eIF2alpha kinase GCN 2 autophosphorylates at Thr 882 and Thr 887 , located in the activation loop at exactly the same positions as Thr 446 and Thr 451 in PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The protein was free of endogenous eIF2alpha kinase activity and was rapidly phosphorylated by the eIF2alpha kinases HCR and PKR . ^^^ The variant eIF2alpha was not phosphorylated by either HCR or PKR , demonstrating that the kinases specifically phosphorylate the correct site in the recombinant protein even in the absence of the other two subunits of the protein . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The negative regulatory effect of human protein kinase RNA regulated ( PKR ) , an eIF2alpha kinase , on virus production was counteracted by PK 2 , indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In cells infected with the herpes simplex virus 1 ( HSV 1 ) recombinant R 3616 lacking both copies of the gamma134 . 5 gene , the double stranded protein kinase R ( PKR ) is activated , eIF 2alpha is phosphorylated , and protein synthesis is shut off . ^^^ Although PKR is also activated in cells infected with the wild type virus , the product of the gamma134 . 5 gene , infected cell protein 34 . 5 ( ICP34 . 5 ) , binds protein phosphatase 1alpha and redirects it to dephosphorylate eIF 2alpha , thus enabling sustained protein synthesis . ^^^ Studies on the wild type parent and mutant viruses showed the following : ( 1 ) PKR was activated in cells infected with parent or mutant virus but not in mock infected cells , consistent with earlier studies ; ( 2 ) lysates of R 3616 , R 5103 , and R 5104 virus infected cells lacked the phosphatase activity specific for eIF 2alpha characteristic of wild type virus infected cells ; and ( 3 ) lysates of R 3616 and R 5103 , which lacked the second site compensatory mutation , contained an activity which phosphorylated eIF 2alpha in vitro , whereas lysates of mock infected cells or cells infected with HSV 1 ( F ) or R 5104 did not phosphorylate eIF 2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Expression and activity of p 67 are induced during heat shock . p 67 , a cellular glycoprotein , protects eIF 2 alpha from phosphorylation by inhibitory kinases such as PKR and HCR . p 67 promoter contains heat shock element ( HSE ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NS5A mediated disruption of PKR dimerization resulted in repression of PKR function and inhibition of PKR mediated eIF 2alpha phosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Activated PKR phosphorylates eIF 2 , an essential initiation factor of protein synthesis , as well as other substrates including histone IIA , a 90 kDa protein from rabbit reticulocytes , the inhibitor , IkappaB , of the transcription factor , NF kappaB , and the HIV 1 Tat protein . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The interferon inducible , double stranded ( ds ) RNA dependent protein kinase ( PKR ) regulates protein synthesis initiation by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Alu RNA is increased by cellular insults and stimulates protein synthesis by inhibiting PKR , the eIF 2 kinase that is regulated by double stranded RNA . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In herpes simplex virus infected cells , viral gamma134 . 5 protein blocks the shutoff of protein synthesis by activated protein kinase R ( PKR ) by directing the protein phosphatase 1alpha to dephosphorylate the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2alpha ) . ^^^ In these cells , PKR is activated but eIF 2alpha is not phosphorylated , and the phosphatase is not redirected to dephosphorylate eIF 2alpha . ^^^ We report the following : ( 1 ) in cells infected with these mutants , US 11 protein was made early in infection ; ( 2 ) US 11 protein bound PKR and was phosphorylated ; ( 3 ) in in vitro assays , US 11 blocked the phosphorylation of eIF 2alpha by PKR activated by poly ( 1 C ) ; and ( 4 ) US 11 was more effective if present in the reaction mixture during the activation of PKR than if added after PKR had been activated by poly ( 1 C ) . ^^^ We conclude the following : ( 1 ) in cells infected with the compensatory mutants , US 11 made early in infection binds to PKR and precludes the phosphorylation of eIF 2alpha , whereas US 11 driven by its natural promoter and expressed late in infection is ineffective ; and ( 2 ) activation of PKR by double stranded RNA is a common impediment countered by most viruses by different mechanisms . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Here we show that ribosomes are inhibitory for PKR activity since they compete with dsRNA for binding to PKR , inhibit the activation of the protein kinase by dsRNA , and prevent the phosphorylation of the PKR substrate eIF2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The human double stranded RNA ( dsRNA ) dependent protein kinase PKR inhibits protein synthesis by phosphorylating translation initiation factor 2alpha ( eIF2alpha ) . ^^^ Expression of PKR in Saccharomyces cerevisiae inhibits protein synthesis by phosphorylation of eIF2alpha , dependent on its two dsRNA binding motifs ( DRBMs ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In mammals , the phosphorylation was shown to be carried out by eIF 2alpha kinases PKR and HRI . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The double stranded RNA ( dsRNA ) activated protein kinase ( PKR ) provides a fundamental control step in the regulation of protein synthesis initiation through phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2alpha ) , a process that prevents polypeptide chain initiation . ^^^ L 18 inhibited both PKR autophosphorylation and PKR mediated phosphorylation of eIF 2alpha in vitro . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Induction of apoptosis due to lowering the level of eukaryotic initiation factor 2 associated protein , p 67 , from mammalian cells by antisense approach . p 67 , a cellular glycoprotein , protects eIF2alpha from phosphorylation by inhibitory kinases such as double stranded RNA dependent eIF 2 kinase , PKR , and heme controlled repressor and thus promotes protein synthesis in mammalian cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PERK has a lumenal domain that is similar to the ER stress sensing lumenal domain of the ER resident kinase Ire 1 , and a cytoplasmic portion that contains a protein kinase domain most similar to that of the known eIF2alpha kinases , PKR and HRI . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Because it has been suggested that PKR might be specifically responsible for producing eIF2alpha ( P ) during reperfusion , we also examined in brain homogenates from wild type and PKR0 / 0 C57BL / 6J 10 129 / SV mice the effect of 5 min of ischemia and 5 min of reperfusion on eIF2alpha ( P ) . ^^^ Our observations contradict hypotheses that PKR activation , loss of eIF2alpha ( P ) phosphatase activity , or any general increase in eIF2alpha kinase activity are responsible for reperfusion induced phosphorylation of eIF2alpha , and we suggest that the mechanism may involve regulation of the availability of eIF2alpha to a kinase . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Viral mutants that lack the GADD 34 related function grow poorly on a variety of malignant human cells , as activation of the cellular PKR kinase leads to the accumulation of inactive , phosphorylated eIF 2 at late times postinfection . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The topics covered include the significance of the regulation and overexpression of polypeptide chain initiation factors for cell transformation and malignancy , the role of mRNA structure in the control of synthesis of key growth regulatory proteins , the actions of the eIF 2 alpha specific protein kinase PKR in the control cell growth and apoptosis , and the involvement of the elongation factor eEF 1 in oncogenesis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The activity of affinity or immuno purified PKR from MCF 7 , T47D , and BT 20 cells appears to be severely attenuated , as judged by its ability to autophosphorylate , or phosphorylate eIF 2 alpha . ^^^ Deregulation of PKR may therefore provide a mechanism for the development or maintenance of a transformed phenotype of human breast carcinomas , mimicking the effects of manipulation of PKR or eIF 2 activity observed in experimental systems . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The interferon ( IFN ) inducible double stranded ( ds ) RNA dependent protein kinase PKR plays a role in the regulation of gene expression through its capacity to phosphorylate the translation initiation factor eIF 2 and to inhibit protein synthesis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The double stranded RNA activated protein kinase PKR is a serine / threonine kinase that modulates protein synthesis through the phosphorylation of translation initiation factor eIF 2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The activated PKR catalyzed phosphorylation of the alpha subunit of eucaryotic translation initiation factor 2 ( eIF2alpha ) . ^^^ The defect in virus protein synthesis was well correlated with the level of phosphorylation of PKR and eIF2alpha . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The phosphorylation is carried out in part by three distinct eIF 2alpha kinases including mammalian double stranded RNA dependent eIF 2alpha kinase ( PKR ) and heme regulated inhibitor kinase ( HRI ) , and yeast GCN 2 . ^^^ In contrast to PKR or HRI , which are dependent on autophosphorylation for their kinase activity , a point mutation that replaced the conserved Lys 614 with an alanine completely abolished the eIF 2alpha kinase activity , whereas the mutant PEK was still autophosphorylated when expressed in Sf 9 cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NS5A blocked viral double stranded RNA ( dsRNA ) induced PKR activation and phosphorylation of eIF 2alpha in IFN treated cells , resulting in high levels of VSV mRNA translation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Eukaryotic translation initiation factor 2alpha ( eIF 2alpha ) , a target molecule of the interferon inducible double stranded RNA dependent protein kinase ( PKR ) , was cleaved in apoptotic Saos 2 cells on treatment with poly ( 1 ) . poly ( C ) or tumour necrosis factor alpha . ^^^ PKR phosphorylates eIF 2alpha on Ser ( 51 ) , resulting in the suppression of protein synthesis . ^^^ PKR mediated translational suppression was repressed when the C terminally cleaved product of eIF 2alpha was overexpressed in Saos 2 cells , even though PKR can phosphorylate this cleaved product . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
These effects have been correlated with phosphorylation of the eukaryotic initiation factor eIF 2alpha and the NF kappaB inhibitor IkappaB , although it has not been demonstrated that IkappaB is a direct target of PKR in vivo . ^^^ Upon induction of PKR in the presence of isopropyl beta D thiogalactoside ( IPTG ) , the 68 kDA wt enzyme and eIF 2alpha are phosphorylated . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The translation initiation factor eIF 2alpha ( alpha subunit of eukaryotic translation initiation factor 2 ) and IkappaBalpha , the inhibitor of the transcription factor NF kappaB , have been proposed as downstream mediators of PKR effects . ^^^ To evaluate the involvement of NF kappaB and eIF 2alpha in the induction of apoptosis by PKR , we have used vaccinia virus ( 10 ) recombinants that inducibly express PKR concomitantly with a dominant negative mutant of eIF 2alpha or a repressor form of IkappaBalpha . ^^^ We found that while expression of PKR by a 10 vector resulted in extensive inhibition of protein synthesis and induction of apoptosis , coexpression of PKR with a dominant negative mutant of eIF 2alpha ( Ser 51 > Ala ) reversed both the PKR mediated translational block and PKR induced apoptosis . ^^^ Our findings provide direct evidence for the involvement of eIF 2alpha and NF kappaB in the induction of apoptosis by PKR . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Although its phosphorylation is specific because it displaces eIF 2 phosphorylation , and the presence of staurosporine prevents its phosphorylation by other serine / threonine kinases , it is a rather poor substrate for PKR . . ^^^ We studied the effect of staurosporine on two well characterised mammalian eIF 2alpha kinases , the heme regulated translational inhibitor ( HRI ) , and interferon inducible double stranded RNA activated protein kinase ( PKR ) . ^^^ In the presence of 0 . 25 microM staurosporine ( a concentration which completely inhibits a wide range of Ser / Thr protein kinases ) , the phosphorylation of eIF 2alpha by HRI and PKR was not inhibited . ^^^ The lack of response of eIF 2alpha kinases to staurosporine allowed us to measure PKR activity in salt washed postmicrosomal supernatants without previous purification of the enzyme . ^^^ In the presence of poly ( 1 ) : poly ( C ) , the PKR activator , we detected both an increased phosphorylation of eIF 2alpha and an increment in the autophosphorylation of PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Whereas the expression of PKR in parental vector transduced clone ( N 2 20P ) is down regulated 48 h after HIV 1 infection , the two transduced clones ( one with PKR in the forward orientation and one in the reverse orientation ) demonstrate increased PKR expression through 96 h post infection , concomitant with an increase in eIF 2alpha phosphorylation and an increase in NF kappaB activity at 72 h postinfection . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Differential phosphorylation of PKR associates with deregulation of eIF 2alpha phosphorylation and altered growth characteristics in 3T3 F442A fibroblasts . ^^^ In a similar manner , evaluation of eIF 2alpha phosphorylation by vertical slab gel iso electric focusing indicated that inactivation of PKR correlated with reduction of eIF 2alpha phosphorylation . ^^^ The reduction in PKR activity and subsequent deregulation of eIF 2alpha phosphorylation was related to appearance of tumor like cellular morphology and increased cell density as shown by cell counts and [ 3H ] thymidine uptake . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Three different eIF2alpha kinases have been identified in mammalian cells , the heme regulated inhibitor ( HRI ) , the interferon inducible RNA dependent kinase ( PKR ) and the endoplasmic reticulum resident kinase ( PERK ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The mammalian kinases PKR and HRI and the yeast kinase GCN 2 specifically phosphorylate Ser 51 on the alpha subunit of the translation initiation factor eIF 2 . ^^^ In addition , both PKR and HRI were found to phosphorylate eIF2alpha S51Y and stimulate GCN 4 expression . ^^^ Isoelectric focusing analysis of eIF2alpha followed by detection using anti eIF2alpha and anti phosphotyrosine specific antibodies demonstrated that PKR and HRI phosphorylated eIF2alpha S51Y on Tyr in vivo . ^^^ These results provide new insights into the substrate recognition properties of the eIF2alpha kinases , and they are intriguing considering the potential for alternate substrates for PKR in cellular signaling and growth control pathways . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
This results in inhibition of protein synthesis via the phosphorylation of eIF2alpha and also induces transcription of inflammatory genes by PKR dependent signaling of the activation of different transcription factors . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Three mammalian eIF2alpha kinases have been identified : the interferon inducible double stranded RNA dependent kinase ( PKR ) , the heme regulated inhibitor ( HRI ) , and the very recently discovered PERK / PEK . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We now demonstrate that recombinant wheat wild type ( 51S ) but not mutant 51 Ala ( 51A ) protein is phosphorylated by human PKR and yeast GCN 2 , which are defined eIF2alpha kinases . ^^^ Plant PKR and GCN 2 phosphorylate recombinant yeast eIF2alpha 51S but not the 51A mutant demonstrating that pPKR has recognition site capability similar to established eIF2alpha kinases . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Alignment of amino acid sequences of Tat and eIF 2alpha indicates similarity between the Tat PKR binding region and the residues around the eIF 2alpha phosphorylation site , suggesting that Tat and eIF 2alpha may bind to the same site on PKR . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Furthermore , we found that vaccinia virus K3L protein , an inhibitor of the eIF 2alpha kinase PKR involved in an anti viral defence pathway , also reduced PEK activity . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
These transformants could be rescued by overexpression of the alpha subunit of wild type eukaryotic translation initiation factor 2 ( eIF2alpha ) , one of the known substrates for PKR . ^^^ We hypothesize that competing heterodimers between p 74 K296R PKR and eIF2alpha K296R PKR may control cell growth such that stabilization of the p 74 K296R PKR heterodimer induces abnormal morphology and cell death . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR phosphorylates eIF 2 alpha and shuts off protein synthesis . gamma 134 . 5 protein binds protein phosphatase 1 and redirects it to dephosphorylate eIF 2 alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The double stranded ( ds ) RNA activated protein kinase PKR is an interferon ( IFN ) inducible serine / threonine protein that regulates protein synthesis through the phosphorylation of the alpha subunit of translation initiation factor 2 ( eIF 2alpha ) . ^^^ Here we show that PKR activation and phosphorylation of eIF 2alpha are both diminished in various virus transformed and nontransformed human T cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Here it is shown that the HCV envelope protein E 2 contains a sequence identical with phosphorylation sites of the interferon inducible protein kinase PKR and the translation initiation factor eIF2alpha , a target of PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
RNA dependent protein kinase ( PKR ) is an interferon induced , RNA activated enzyme that phosphorylates and inhibits the function of the translation initiation factor eIF 2 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The double stranded RNA dependent protein kinase PKR has been shown to phosphorylate eukaryotic initiation factor 2 alpha ( eIF 2alpha ) , a well characterized factor for down regulating protein synthesis , in response to environmental stress conditions . ^^^ Hyperphosphorylated eIF 2alpha was increased in selected tissues from older mice compared with tissues from younger mice indicating a possible correlation between PKR expression and kinase function . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The nonstructural 5A ( NS5A ) protein of HCV has been reported to inhibit PKR , an IFN induced kinase involved in the antiviral action of IFN , at the level of control of protein synthesis through the phosphorylation of the initiation factor eIF2alpha ( M . ^^^ The effect of expression of HCV proteins on PKR activity was assayed in a reporter assay and by direct analysis of the in vivo phosphorylation of eIF2alpha after treatment of cells with poly ( 1 ) poly ( C ) . ^^^ We found that neither PKR activity nor eIF2alpha phosphorylation was affected by coexpression of the HCV proteins . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The interferon ( IFN ) induced double stranded RNA activated protein kinase PKR mediates inhibition of protein synthesis through phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF2alpha ) and is also involved in the induction of the IFN gene through the activation of the transcription factor NF kappaB . ^^^ Here , we have studied the ability of PKR to activate NF kappaB in a reporter assay and have shown for the first time that two catalytically inactive PKR mutants , PKR / KR296 and a deletion mutant ( PKR / Del42 ) which lacks the potential eIF2alpha binding domain , can also activate NF kappaB . ^^^ This result indicated that NF kappaB activation by PKR does not require its kinase activity and that it is independent of the PKR eIF2alpha relationship . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
To evaluate the in vivo capability of plant eIF2alpha to participate in the translation pathway , we have used vaccinia virus recombinants that constitutively express wheat eIF2alpha and inducibly express the eIF2alpha dsRNA stimulated protein kinase , PKR , in BSC 40 cells . ^^^ Activation of PKR in cells expressing wild type wheat eIF2alpha resulted in an inhibition of cellular and viral protein synthesis and an induction of cellular apoptosis correlating with phosphorylation of eIF2alpha on serine 51 . ^^^ Expression of a nonphosphorylatable mutant ( 51A ) of plant eIF2alpha reversed the PKR mediated translational block as well as the PKR induced apoptosis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR is a cellular serine / threonine kinase that phosphorylates eukaryotic translation initiation factor 2alpha ( eIF2alpha ) to regulate protein synthesis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The RNA dependent protein kinase ( PKR ) is an interferon induced , RNA activated enzyme that phos phorylates the alpha subunit of the translation initiation factor eIF 2 , inhibiting its function . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Activated PKR phosphorylates its cellular substrate , eIF 2 , an essential initiation factor of translation . ^^^ On the contrary , PKR autophosphorylation and the phosphorylation of its substrate , the alpha subunit of eIF 2 , is 7 40 fold higher in lysates prepared from breast carcinoma cell lines than in those from nontransformed epithelial cell lines . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We show that PKR and mTOR signaling pathways control the ratio of C / EBP isoform expression through the eukaryotic translation initiation factors eIF 2alpha and eIF 4E , respectively . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Our data indicate that in normal cells , PKR primarily prevents virus replication by inhibiting the translation of viral mRNAs through phosphorylation of eIF2alpha , while concomitantly assisting in the production of autocrine IFN and the establishment of an antiviral state . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Apoptosis induction by PKR involves phosphorylation of the translational factor eIF 2alpha and activation of the transcriptional factor NF kappaB , but caspase pathways activated by PKR are not known . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Overexpression of PACT in mammalian cells leads to phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 ( eIF2alpha ) , the cellular substrate for PKR , and leads to inhibition of protein synthesis . ^^^ PACT mediated activation of PKR leads to enhanced eIF2alpha phosphorylation followed by apoptosis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The interferon induced protein kinase PKR is activated upon binding double stranded RNA and phosphorylates the translation initiation factor eIF2alpha on Ser 51 to inhibit protein synthesis in virally infected cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Both mutants decreased eIF2alpha phosphorylation occurring in hemin and poly ( IC ) treated reticulocyte lysates due to the activation of double stranded RNA dependent protein kinase ( PKR ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Upon activation by double stranded RNA in virus infected cells , the cellular PKR kinase phosphorylates the translation initiation factor eukaryotic initiation factor 2 ( eIF 2 ) and thereby inhibits protein synthesis . ^^^ While the gamma 34 . 5 gene specifies a regulatory subunit for protein phosphatase 1 alpha , the Us 11 gene encodes an RNA binding protein that also prevents PKR activation . gamma 34 . 5 mutants fail to grow on a variety of human cells as phosphorylated eIF 2 accumulates and protein synthesis ceases prior to the completion of the viral life cycle . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The PKR ( protein kinase dsRNA induced ) kinase phosphorylates and inhibits the eukaryotic initiator of translation eIF 2alpha leading again to apoptosis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In contrast , the protein kinase PKR , which is responsible for the phosphorylation and consequent inhibition of eIF2alpha activity , was specifically overexpressed in activated SLE T cells , correlating with an increase in eIF2alpha phosphorylation . ^^^ Therefore , high expression of PKR and subsequent eIF2alpha phosphorylation is likely responsible , at least in part , for impaired translational and proliferative responses to mitogens in T cells from SLE patients . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
A cellular 67 kDa glycoprotein ( p 67 ) has been proposed to have an important role in regulating the activity of eIF2alpha kinases including the interferon induced , dsRNA stimulated protein kinase PKR . ^^^ These effects correlated with decreased eIF2alpha phosphorylation , with rescue of PKR mediated inhibition of protein synthesis , and with partial inhibition of PKR triggered activation of NF kappaB . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
No changes in the PKR endoplasmic reticulum related kinase or eIF 2 alpha phosphatase were found . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Consistent with bypassing eIF2B , these conditions also suppress the lethal effect of overexpressing the mammalian tumor suppressor PKR , an eIF2alpha kinase . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The alpha subunit of eukaryotic initiation factor eIF 2 is a preferred substrate for the double stranded RNA activated protein kinase , PKR . ^^^ Early studies provided evidence implicating PKR as the kinase that phosphorylates eIF2alpha under conditions of cell stress such as the accumulation of misfolded proteins in the lumen of the endoplasmic reticulum , i . e . , the unfolded protein response ( UPR ) . ^^^ However , the recent identification of a trans microsomal membrane eIF2alpha kinase , termed PEK or PERK , suggests that this kinase , and not PKR , might be the kinase that is activated by misfolded protein accumulation . ^^^ In a similar manner , we find that during amino acid deprivation the inhibition of protein synthesis and extent of increase in eIF2alpha phosphorylation are identical in wildtype and PKR KO cells . ^^^ Overall , the results show that PKR is not required for increased eIF2alpha phosphorylation or inhibition of protein synthesis under conditions promoting the UPR or in response to amino acid deprivation . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Inhibitory sequences in the N terminus of the double stranded RNA dependent protein kinase , PKR , are important for regulating phosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) . ^^^ During viral infection , phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF2alpha ) by the interferon induced RNA dependent protein kinase , PKR , leads to inhibition of translation initiation and viral proliferation . ^^^ The catalytic rate of eIF2alpha phosphorylation by our purified PKR was increased in response to dsRNA , but not single stranded RNA or DNA , consistent with the properties previously described for PKR purified from mammalian sources . ^^^ While both dsRBD 1 and dsRBD 2 were required for activation of PKR by dsRNA , only deletion of dsRBD 1 severely reduced the basal eIF2alpha kinase activity . ^^^ Heparin , a known in vitro activator of PKR , enhanced eIF2alpha phosphorylation by PKR mutants lacking their entire N terminal sequences , including the dsRBDs . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR inhibits translation initiation through the phosphorylation of the alpha subunit of the initiation factor eIF 2 ( eIF 2 alpha ) and also controls the activation of several transcription factors such as NF kappa B , p 53 , or STATs . ^^^ The mechanism of apoptosis induction by PKR involves phosphorylation of eIF 2 alpha and activation of NF kappa B . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The mechanism of viral oncolytic activity involved the induction of multiple caspase dependent apoptotic pathways was effective in the absence of any significant cytotoxic T lymphocyte response , and occurred despite normal PKR activity and eIF2alpha phosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Translation inhibition in apoptosis : caspase dependent PKR activation and eIF 2 alpha phosphorylation . ^^^ The protein kinase PKR is a major player in the cellular antiviral response , acting mainly by phosphorylation of the alpha subunit of the eukaryotic translation initiation factor 2 ( eIF 2 alpha ) to block de novo protein synthesis . ^^^ Since several reports have demonstrated that translation is inhibited in apoptosis , we investigated whether PKR and eIF 2 alpha phosphorylation contribute to this process . ^^^ We show that PKR is proteolysed and that eIF 2 alpha is phosphorylated at the early stages of apoptosis induced by various stimuli . ^^^ Our results demonstrate a new and caspase dependent activation mode for PKR , leading to eIF 2 alpha phosphorylation and translation inhibition in apoptosis . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR mediates the host IFN induced antiviral response at least in part by inhibiting mRNA translation initiation through phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF2alpha ) . ^^^ Accordingly , infection of IFN pretreated HeLa S 3 cells with an E3L deficient 10 ( VVDeltaE3L ) resulted in increased phosphorylation levels of both PKR and eIF2alpha . ^^^ IFN pretreated cells infected with 10 in which the E3L locus was replaced with the NS5A gene ( VVNS5A ) displayed diminished phosphorylation of PKR and eIF2alpha in a transient manner . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
However , in all reperfused groups , the RNA dependent protein kinase ( PKR ) like endoplasmic reticulum eIF2alpha kinase ( PERK ) exhibited an isoform mobility shift on SDS PAGE , consistent with the activation of the kinase . ^^^ These data indicate that neither HRI nor GCN 2 are required for the large increase in post ischemic brain eIF2alpha ( P ) , and in conjunction with our previous report that eIF2alpha ( P ) is produced in the brain of reperfused PKR / mice , provides evidence that PERK is the kinase responsible for eIF2alpha phosphorylation in the early post ischemic brain . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
K3L inhibited both autophosphorylation of PKR and phosphorylation of eIF 2 alpha , whereas VAI RNA inhibited only autophosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The RNA dependent protein kinase ( PKR ) is an interferon induced , RNA activated enzyme that phosphorylates the alpha subunit of eukaryotic initiation factor 2 ( eIF2alpha ) , inhibiting the function of the eIF 2 complex and continued initiation of translation . ^^^ This autophosphorylation reaction stimulates the eIF2alpha kinase activity of PKR . ^^^ These results are consistent with an activation mechanism that includes release of the activating RNA upon autophosphorylation of PKR prior to phosphorylation of eIF2alpha . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Two genomic regions of hepatitis C virus ( HCV ) , the interferon sensitivity determining region ( ISDR ) of the non structural 5A gene ( NS5A ) and the protein kinase RNA activated ( PKR ) eukariotic transcription factor ( eIF 2 alpha ) phosphorylation homology domain ( PePHD ) of the structural E 2 gene , interact in vitro with the interferon inducible cellular PKR protein kinase . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We show that this association in fact augments the autophosphorylation of PKR and the phosphorylation of the translation initiation factor eIF2alpha , which are two markers of PKR activity . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We found that MC159L is not a direct inhibitor of PKR since it does not associate with PKR and can not block PKR induced phosphorylation of eIF 2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR is a member of a small family of kinases that are activated by extracellular stresses and that phosphorylate the alpha subunit of protein synthesis initiation factor eIF 2 , thereby inhibiting protein synthesis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The mammalian IFN inducible eIF2alpha kinase , PKR , rescues starvation induced autophagy in GCN 2 disrupted yeast , and pkr null and Ser 51 nonphosphorylatable mutant eIF2alpha murine embryonic fibroblasts are defective in autophagy triggered by herpes simplex virus infection . ^^^ Furthermore , PKR and eIF2alpha Ser 51 dependent autophagy is antagonized by the herpes simplex virus neurovirulence protein , ICP34 . 5 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Earlier studies have shown that herpes simplex virus type 1 ( HSV 1 ) activated protein kinase R ( PKR ) but that the product of the product of the gamma ( 1 ) 34 . 5 gene binds and redirects the host phosphatase 1 to dephosphorylate the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2alpha ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In response to cellular stress such as viral infections , eIF 2alpha is phosphorylated by double stranded RNA dependent protein kinase ( PKR ) leading to the inhibition of cellular protein synthesis . ^^^ The importance of eIF 2alpha as a regulatory mechanism for protein synthesis is illustrated by the wide variety of strategies employed by viruses to down regulate PKR . ^^^ Thus , Vaccinia virus encodes K3L protein , which resembles eIF 2alpha and acts as a pseudo substrate inhibitor of PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The PKR inhibitor 2 aminopurine prevented the Poly ( IC ) stimulation of eIF 2 alpha phosphorylation and the Poly ( IC ) mediated decrease in IGF 1 mRNA . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR , an interferon ( IFN ) inducible protein kinase activated by double stranded RNA , inhibits translation by phosphorylating the initiation factor eIF2alpha chain . ^^^ Nonphosphorylatable mutant eIF2alpha , knockout of PKR and PKR inhibitors 2 aminopurine , transdominant negative PKR , or vaccinia E3L correspondingly enhances translation of IFN gamma mRNA . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Further , in vitro studies demonstrated that a recombinant expressed U ( S ) 11 protein binds PKR , blocks the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2alpha ) by activated PKR , and , if provided prior to PKR activation , precluded PKR autophosphorylation . ^^^ The results suggest that the U ( S ) 11 interaction with PKR at the ribosome is RNA dependent and that the U ( S ) 11 protein contains a substrate domain with homology to eIF 2alpha in close proximity to an essential binding domain . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Three stresses were studied that cause the phosphorylation of the translation initiation factor , eIF2alpha , by activating specific kinases : ( 1 ) amino acid starvation , which activates GCN 2 ; ( 2 ) endoplasmic reticulum ( ER ) stress , which activates PKR like ER kinase , PERK kinase ; and ( 3 ) double stranded RNA , which activates double stranded RNA dependent protein kinase ( PKR ) by mimicking viral infection . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The RNA dependent protein kinase ( PKR ) is an interferon induced , RNA activated enzyme that phosphorylates and inhibits the function of the translation initiation factor eIF 2 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Upon virus infection , PKR can , as part of the host defense system , inhibit mRNA translation by phosphorylating the alpha subunit of protein synthesis eukaryotic initiation factor 2 ( eIF 2alpha ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We report that Ad mda 7 induces andactivates the double stranded RNA dependent protein kinase ( PKR ) , which leads to phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2alpha ) and the induction of apoptosis in lung cancer cells . ^^^ Treatment with 2 aminopurine ( 2 AP ) , a serine / threonine kinase inhibitor , inhibits PKR activation , eIF2alpha phosphorylation , and apoptosis induction by Ad mda 7 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Furthermore , IRES use is decreased by over expression of the dominant negative form of the eIF 2 alpha kinase , PKR , the vaccinia virus K3L gene , or the eIF 2 alpha S51A variant which result in decreased eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Analysis included the E 2 PKR eIF 2alpha phosphorylation homology domain ( PePHD , codons 659 670 ) , where the sequence was well conserved , and codons 2001 2420 of NS5A . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The sensitivity or resistance of the virus to IFN has been linked to certain types of the interferon sensitivity determining region ( ISDR ) and PKR eIF2alpha phosphorylation homology domain ( PePHD ) sequences in the NS5A and E 2 regions of the viral genome , respectively . ^^^ The PKR expression level was enhanced by IFN in all cells , but eIF2alpha phosphorylation level was not changed , probably due to the absence of double stranded RNA species . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In response to stress signals , including virus infection , the normally latent PKR becomes activated through autophosphorylation and dimerization and phosphorylates the eIF2alpha translation initiation factor subunit , leading to an inhibition of mRNA translation initiation . ^^^ Overexpression of PKR in yeast also leads to an inhibition of eIF2alpha dependent protein synthesis , resulting in severe growth suppression . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PACT expression also coincides with the presence of active PKR and phosphorylated eIF2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
K3L is a structural mimic of PKR ' s natural substrate , the translation initiation factor eIF2alpha . ^^^ Further analysis reveals that PKR dimerization composes a key switch that regulates both its catalytic activation and its molecular recognition of K3L and eIF2alpha . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Here we show that adenovirus mediated E2F 1 overexpression in cancer cells induces expression and autophosphorylation of the double stranded RNA dependent protein kinase PKR leading to phosphorylation of its downstream target , the alpha subunit of the eukaryotic translation initiation factor 2 ( eIF 2alpha ) and to apoptotic cell death . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
METHODS : HuH 7 cells were infected or transfected with p 48 gene expression adenoviral vector or plasmid vector , respectively , and incubated with or without IFN alpha , then PKR expression and phosphorylation of alpha subunit of eukaryotic protein synthesis initiation factor 2 ( eIF2alpha ) in the cells were examined . ^^^ However , p 48 overexpression in combination with interferon alpha treatment caused a marked increase in PKR expression and augmented the phosphorylation of eIF2alpha , by which the transfected CAT gene translation , as well as the endogenous alpha fetoprotein synthesis , was blocked without affecting their mRNA levels . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Overexpression of Hri1p , Hri2p , or the human eIF2alpha kinase , double stranded RNA dependent protein kinase ( PKR ) , impeded growth of S . pombe due to elevated phosphorylation of eIF2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Both the charged domain of P 52 ( rIPK ) and the TPR 7 domain of P 58 ( IPK ) were required for P 52 ( rIPK ) to mediate downstream control of PKR activity , eIF2alpha phosphorylation , and cell growth . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Treatment of cells with 15d PGJ ( 2 ) results in strong induction of heat shock protein 70 ( HSP 70 ) gene expression , suggesting that 15d PGJ ( 2 ) might activate protein kinase R ( PKR ) , an eIF 2alpha kinase shown previously to be responsive to agents that induce stress . 15d PGJ ( 2 ) strongly stimulates eIF 2alpha phosphorylation and down regulates cyclin D 1 expression in a cell line derived from wild type mouse embryo fibroblasts but has an attenuated effect in PKR null cells , providing evidence that PKR is involved in mediating the effect of 15d PGJ ( 2 ) on eIF 2alpha phosphorylation and cyclin D 1 expression . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
M156R , the product of the myxoma virus M156R open reading frame , has sequence similarity to eIF2alpha as well as to a family of viral proteins that bind to the interferon induced protein kinase PKR and inhibit phosphorylation of eIF2alpha . ^^^ M156R is an efficient substrate for phosphorylation by PKR and can compete with eIF2alpha . ^^^ The similarity between M156R and the beta barrel structure in the N terminus of eIF2alpha suggests that the viral homologs mimic eIF2alpha structure in order to compete for binding to PKR . ^^^ Comparison of the structures of the K3L model , M156R , and human eIF2alpha indicated that residues important for binding to PKR are located at conserved positions on the surface of the beta barrel and in the mobile loop , identifying the putative PKR recognition motif . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
While double stranded RNA dependent protein kinase ( PKR ) is named as it is activated by double stranded RNA produced by virus , its activation induces an inhibition of protein translation and apoptosis via the phosphorylation of the eukaryotic initiation factor 2alpha ( eIF2alpha ) . ^^^ Here we show that PKR activation and eIF2alpha phosphorylation play a significant role in apoptosis of neuroblastoma cells and primary neuronal cultures induced by the beta amyloid ( Abeta ) peptides , the calcium ionophore A 23187 and flavonoids . ^^^ The phosphorylation of eIF2alpha and the number of apoptotic cells were enhanced in over expressed wild type PKR neuroblastoma cells exposed to Abeta peptide , while dominant negative PKR reduced eIF2alpha phosphorylation and apoptosis induced by Abeta peptide . ^^^ Activation of PKR and eIF2alpha pathway by Abeta peptide are triggered by an increase in intracellular calcium because the intracellular calcium chelator BAPTA AM significantly reduced PKR phosphorylation . ^^^ Taken together , these results reveal that PKR and eIF2alpha phosphorylation could be involved in the molecular signalling events leading to neuronal apoptosis and death and could be a new target in neuroprotection . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
P 58 ( IPK ) is an Hsp 40 family member known to inhibit the interferon ( IFN ) induced , double stranded RNA activated , eukaryotic initiation factor 2alpha ( eIF2alpha ) protein kinase R ( PKR ) by binding to its kinase domain . ^^^ P 58 ( IPK ) interacts with and inhibits the PKR like ER localized eIF2alpha kinase PERK , which is normally activated during the ER stress response to protect cells from ER stress by attenuating protein synthesis and reducing ER client protein load . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The interferon ( IFN ) inducible protein kinase PKR plays an important role in cell defense against virus infection by impairing protein synthesis as a result of eIF 2alpha phosphorylation . ^^^ Here , we show that expression of the viral nonstructural ( NS ) and PKR proteins and eIF 2alpha phosphorylation are all variably regulated in proliferating replicon Huh 7 cells . ^^^ In proliferating cells , induction of PKR protein by IFN alpha is inversely proportional to viral RNA replication and NS protein expression , whereas eIF 2alpha phosphorylation is induced by IFN alpha in proliferating but not in serum starved replicon cells . ^^^ The role of PKR and eIF 2alpha phosphorylation was further addressed in transient expression assays in Huh 7 cells . ^^^ These experiments demonstrated that activation of PKR results in the inhibition of EMCV IRES driven NS protein synthesis from the subgenomic viral clone through mechanisms that are independent of eIF 2alpha phosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Eukaryotic cells express a family of eukaryotic translation initiation factor 2 alpha ( eIF2alpha ) kinases ( eg , PKR , PERK PEK , GCN 2 , HRI ) that are individually activated in response to distinct types of environmental stress . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Moreover , both recombinant rainbow trout and zebrafish eIF2alphas can be phosphorylated in vitro by the mammalian heme sensitive eIF2alpha kinase , HRI / HCR , as well as the interferon inducible , dsRNA sensitive kinase , PKR . ^^^ These data imply that RTG 2 cells express the interferon induced eIF2alpha kinase , PKR and suggests that the interferon / eIF2alpha / PKR response to virus infection may be a conserved vertebrate characteristic . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The hepatitis C virus envelope protein , E 2 , is an endoplasmic reticulum ( ER ) bound protein that contains a region of sequence homology with the double stranded RNA activated protein kinase PKR and its substrate , the eukaryotic translation initiation factor 2 ( eIF 2 ) . ^^^ We previously reported that E 2 modulates global translation through inhibition of the interferon induced antiviral protein PKR through its PKR eIF2alpha phosphorylation site homology domain ( PePHD ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Binding to dsRNA activates PKR that phosphorylates the eukaryotic initiation factor eIF 2alpha leading to protein synthesis inhibition . ^^^ Addition of TRBP restored translation efficiency of TAR CAT RNA and decreased the phosphorylation status of eIF 2alpha , confirming its role as a PKR inhibitor . ^^^ TRBP inhibited eIF 2alpha phosphorylation in both cases , suggesting that it restores the translation of TAR CAT RNA independently and in addition to its ability to inhibit PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Downstream effectors of PKR include the translation initiation factor , eIF2alpha , and the transcription factor , NF kappaB . ^^^ We found elevated levels of PKR protein , dsRNA dependent PKR autophosphorylation activity , and phosphorylated eIF2alpha in melanoma cells compared to nontransformed melanocytes in culture . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
This phenomenon was also observed for the immunohistochemical staining of phosphorylated PKR ( double stranded RNA dependent protein kinase ) , the upstream kinase for eIF2alpha . ^^^ Activation of PKR eIF2alpha pathway is considered to be pro apoptotic . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
During the interferon ( IFN ) response , translational repression due to phosphorylation of eukaryotic initiation factor 2alpha , eIF2alpha , by the double stranded RNA dependent protein kinase , PKR , constitutes a means of inhibiting viral replication . ^^^ During the IFN antiviral response in RNase L null cells , PKR mRNA stability was enhanced , PKR induction was increased , and the phosphorylated form of eIF2alpha appeared with extended kinetics compared with similarly treated wild type cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
HCV protein synthesis is thus potentially sensitive to the inhibition of eIF 2 activity that can result from the phosphorylation of the latter by the interferon inducible , double stranded RNA activated protein kinase PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We have demonstrated previously that Abeta peptide induces activation of double stranded RNA dependent serine / threonine protein kinase ( PKR ) and phosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) in neurons in vitro . ^^^ Degenerating neurons in brain tissues from Alzheimer ' s disease patients also displayed high immunoreactivity for phosphorylated PKR and eIF2alpha . ^^^ We report here that inhibition of caspase 3 activity reduces phosphorylation of PKR and to a certain extent , cleavage of PKR and eIF2alpha in neurons exposed to Abeta peptide . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We conclude that IFN blocks HCV replication through translational control programs involving PKR and P 56 to , respectively , target eIF 2 and eIF 3 dependent steps in the viral RNA translation initiation process . . ^^^ However , within cells expressing an NS5A variant that inhibited PKR , we observed a reduced level of eukaryotic initiation factor 2 alpha subunit ( eIF2alpha ) phosphorylation and a concomitant increase in HCV protein synthetic rates , enhancement of viral RNA replication , and a partial rescue of viral internal ribosome entry site ( IRES ) function from IFN suppression . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Cellular responses to dsRNA include induction of alpha / beta interferon ( IFN ) synthesis and activation of the enzyme PKR , which exerts its antiviral effect by phosphorylating the eukaryotic initiation factor eIF 2 alpha , thereby inhibiting translation . ^^^ We show that wild type ( wt ) BUNV that expresses NSs triggered PKR dependent phosphorylation of eIF 2 alpha to levels similar to those of a recombinant virus that does not express NSs ( BUNdelNSs virus ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The phosphorylation state of PKR and its downstream target , eIF2alpha , were unaffected by either IFN gamma or VSV infection . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
LANA 2 also counteracted the PKR mediated inhibition of protein synthesis and partially blocked PKR induced phosphorylation of eIF 2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
DON rapidly activated PKR within 1 to 5 min , as evidenced by autophosphorylation and by phosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Ectopic , immediate early Us 11 expression prevents eIF2alpha phosphorylation and the inhibition of translation observed in cells infected with a gamma ( 1 ) 34 . 5 mutant by inhibiting activation of the cellular kinase PKR and the subsequent phosphorylation of eIF2alpha ; however , a requirement for the Us 11 protein , produced in its natural context as a gamma ( 2 ) polypeptide , remains to be demonstrated . ^^^ In cells infected with a Us 11 mutant , elevated levels of activated PKR and phosphorylated eIF2alpha were detected , viral translation rates were reduced 6 to 7 fold , and viral replication was reduced 13 fold compared to replication in cells infected with either wild type virus or a virus in which the Us 11 mutation was repaired . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The second function , encoded by the product of the Us 11 gene , specifies a double stranded RNA binding protein that prevents activation of PKR , a cellular eIF2alpha kinase . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Subsequent studies revealed normal dsRNA dependent protein kinase ( PKR ) activation and phosphorylation of eukaryotic initiation factor 2 ( eIF 2 ) alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Cell death is then induced by PKR through the phosphorylation of eIF 2alpha . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We have investigated a possible functional relationship between the E 6 oncoprotein and eIF2alpha phosphorylation by an inducible dimerization form of the IFN inducible protein kinase PKR . ^^^ These findings demonstrate , for the first time , a role of the oncogenic E 6 in apoptotic signaling induced by PKR and eIF2alpha phosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
This review will describe recent aspects of the mechanisms involved , with particular emphasis on the regulation of the eIF 2 alpha kinase PKR and the control of 4E BP phosphorylation by viral gene products , growth inhibitory cytokines and the tumour suppressor protein p53 . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Protein kinase R ( PKR ) and eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) undergo phosphorylation in response to stress , and the phosphorylated forms of these proteins play a key role in regulating protein synthesis . ^^^ The objective of this study was to investigate the expression profile of phospho PKR and phospho eIF 2 alpha during the course of EAE in order to advance the understanding of the stress response in this disease . ^^^ Alternatively , phospho PKR and phospho eIF 2 alpha may promote apoptosis as a way to regulate T cell number in the CNS . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Previous reports demonstrate that following stress , RAX / PACT associates with and activates PKR resulting in eIF2alpha phosphorylation , consequent translation inhibition , and cell death via apoptosis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
BLAST search reveals that the putative CaPKR like protein is most homologous to human PKR and also has a high level homology with all members of a family of eIF2alpha kinases . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Once bound to viral dsRNA , PKR becomes activated and phosphorylates eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) leading to the cessation of host cell translation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
OBJECTIVE : Protein kinase R ( PKR ) interacts with dsRNA and phosphorylates eukaryotic initiation factor 2 ( eIF2alpha ) , which in turn inhibits host translation initiation as well as hepatitis C virus ( HCV ) translation . ^^^ RESULTS : PKR protein levels were consistently increased in HCV related HCC compared with NT ( p=0 . 001 ) ; similar increases were seen in total eIF2alpha and the PKR inhibitor p58IPK in T compared with NT ( p=0 . 022 , p=0 . 048 , respectively ) . ^^^ Relative increases in phosphorylated eIF2alpha ( peIF2alpha ) were also seen , and the ratio of peIF2alpha / total eIF2alpha did not change in T compared with NT , suggesting that PKR remains functional within T . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The double stranded ( ds ) RNA activated protein kinase PKR phosphorylates the alpha subunit of the eukaryotic initiation factor 2 ( eIF2alpha ) and inhibits translation initiation . ^^^ We used a solid phase kinase assay system to show that PKR does not transfer its own phosphate to either PKR or eIF2alpha but rather uses the gamma phosphate from ATP . ^^^ The results imply that even though the isolated kinase domain of PKR phosphorylates intact PKR and eIF2alpha , it is unable to activate PKR . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR is a cellular protein kinase activated by double stranded RNA ( dsRNA ) that phosphorylates eukaryotic initiation factor alpha ( eIF2alpha ) and inhibits protein translation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Enhanced phosphorylation of PKR and eIF2alpha was also observed in cells infected with 10 hr and was suppressed by CP 77 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The eIF2alpha kinase PKR has been shown to play an essential role against vesicular stomatitis virus ( VSV ) infection . ^^^ We also show that VSV infected PERK ( / ) MEFs are unable to fully activate PKR , suggesting a cross talk between the two eIF2alpha kinases in virus infected cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Double stranded RNA dependent protein kinase ( PKR ) is a participant in the cellular antiviral response and phosphorylates the alpha subunit of eukaryotic translation initiation factor 2alpha ( eIF 2alpha ) to block protein synthesis . ^^^ To investigate the functional relationship between phosphatases and apoptosis , we examined the phosphorylation levels of PKR and eIF 2alpha by Western blot analysis . ^^^ During treatment of cells with it at the higher concentration ( 100 nM ) , okadaic acid increased the level of phosphorylated PKR in MG 63 cells , this kinase phosphorylating eIF 2alpha . ^^^ Our results also suggest that the inhibition of the protein phosphatase activity by okadaic acid induced apoptosis in MG 63 cells through PKR and eIF 2alpha . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Specifically , we show that TZDs rapidly activate the ER stress responsive pancreatic eukaryotic initiation factor 2alpha ( eIF2alpha ) kinase or PKR ( double stranded RNA activated protein kinase ) like endoplasmic reticulum kinase / pancreatic eIF2alpha kinase , and that activation of these kinases is correlated with subsequent eIF2alpha phosphorylation . ^^^ Interestingly , PPARgamma ligands not only activated calcium / calmodulin dependent kinase 2 ( CaMKII ) 2 fold over control , but the selective CaMKII inhibitor , KN 93 , attenuated MKK3 / 6 and p 38 as well as PKR and eIF2alpha phosphorylation . ^^^ Although CaMKII was not affected by inhibition of PKR with 2 aminopurine , phosphorylation of MKK3 / 6 and p 38 as well as eIF2alpha were significantly reduced . ^^^ Collectively , these data provide evidence that CaMKII is a regulator of PKR dependent p 38 and eIF2alpha phosphorylation in response to ER calcium depletion by TZDs . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
BACKGROUND : The interferon ( IFN ) induced , dsRNA dependent serine / threonine protein kinase , PKR , plays a key regulatory role in the IFN mediated anti viral response by blocking translation in the infected cell by phosphorylating the alpha subunit of elongation factor 2 ( eIF 2 ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Activated PKR then phosphorylates the alpha subunit of the protein synthesis initiation factor 2 ( eIF2alpha ) thereby inducing a general block in the initiation of protein synthesis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In several types of mechanically sensitive , contractile fibroblasts including rat cardiac , human gingival , and Rat 2 fibroblasts , tensile forces increased eIF 2alpha phosphorylation , a downstream effector of PKR . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Although the double stranded RNA dependent protein kinase ( PKR ) is activated during HSV infection , the gamma ( 1 ) 34 . 5 protein inhibits the activity of PKR by mediating dephosphorylation of the translation initiation factor eIF 2alpha . ^^^ Further analysis indicates that hyperphosphorylation of eIF 2alpha caused by HSV is greater in PKR+ / + cells than in PKR / cells . ^^^ Together , these observations suggest that regulation of eIF 2alpha phosphorylation by the gamma ( 1 ) 34 . 5 protein is an efficient way to antagonize the inhibitory activity of PKR as well as PERK during productive infection . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The double stranded RNA ( dsRNA ) dependent protein kinase ( PKR ) is induced as part of the IFN response in mammals and acts to shut down protein synthesis by the phosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) . ^^^ Phylogenetic analysis shows that the C terminal kinase domain is more closely related to the kinase domain of PKR than to any of the other three known eIF2alpha kinases . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The rapid drop in protein synthesis observed in apoptosis correlates with caspase dependent breakdown of eukaryotic translation initiation factor ( eIF ) 4G , activation of the double stranded RNA activated protein kinase PKR , and phosphorylation of its substrate eIF 2 alpha . ^^^ In necrosis induced by tumor necrosis factor , double stranded RNA , or viral infection , de novo protein synthesis persists and 28S ribosomal RNA fragmentation , eIF 2 alpha phosphorylation , and proteolytic activation of PKR are absent . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The influenza virus protein NS 1 binds dsRNA and antagonizes induction of PKR activity , an IFN inducible antiviral protein which phosphorylates and inactivates the elongation factor eIF 2alpha , resulting in cessation of translation . ^^^ In NS 1 expressing neuroblastoma cells , VSV replication was inhibited by IFN beta as well as in control NB41A3 cells , and eIF 2alpha phosphorylation was blocked , suggesting that PKR activity was not involved in inhibition of viral protein synthesis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Increased PKR expression and activity ( phosphorylation of eukaryotic initiation factor 2alpha [ eIF2alpha ] ) were demonstrated in PKR transduced , differentiated HSC . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Indeed , the phosphorylation of eIF2alpha by PKR was impaired in Karpas 299 cells . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Although IkappaBalpha was degraded phosphorylation of eIF 2 alpha , a substrate of PKR , did not occur in the mutant cells treated with okadaic acid . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR and GCN 2 kinases and guanine nucleotide exchange factor eukaryotic translation initiation factor 2B ( eIF2B ) recognize overlapping surfaces on eIF2alpha . ^^^ Four stress responsive protein kinases , including GCN 2 and PKR , phosphorylate eukaryotic translation initiation factor 2alpha ( eIF2alpha ) on Ser 51 to regulate general and gene specific protein synthesis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
An interaction between the protein kinase ( PKR ) eIF 2 alpha phosphorylation homology domain ( PePHD ) within the E 2 protein of hepatitis C virus ( HCV ) and cell protein kinase ( PKR ) may affect the control of protein synthesis and cell growth . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
GB virus type C NS5A sequence polymorphisms : association with interferon susceptibility and inhibition of PKR mediated eIF2alpha phosphorylation . ^^^ Using a yeast genetic system , IFN resistant NS5A inhibited PKR mediated phosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) in yeast , whereas IFN sensitive NS5A did not inhibit PKR function . ^^^ GBV C NS5A amino acid polymorphisms appear to be involved in response to IFN therapy , and IFN resistant GBV C NS5A inhibited PKR mediated eIF2alpha phosphorylation in a yeast genetic system , suggesting a mechanism by which GBV C may evade clearance by naturally occurring host antiviral responses . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Moreover , we observe that the overexpression of the viral protein induces an upregulation of PKR activity , which does not correlate with an increased eIF 2 phosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Using Western blot analysis and real time qPCR , we determined that neonatal rat astrocyte cultures constitutively express TLR 3 mRNA and protein , and that PIC dsRNA induced phosphorylation of eIF2alpha , as well as mRNA type 1 interferon ( alpha / beta IFN ) response genes Mx 1 , PKR , and TLR 3 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In response to binding viral double stranded RNA byproducts within a cell , the RNA dependent protein kinase PKR phosphorylates the alpha subunit of the translation initiation factor eIF 2 on a regulatory site , Ser 51 . ^^^ Higher order substrate recognition of eIF2alpha by the RNA dependent protein kinase PKR . ^^^ To understand the basis for substrate recognition by and the regulation of PKR , we determined 10 ray crystal structures of the catalytic domain of PKR in complex with eIF2alpha . ^^^ In addition to inducing a local unfolding of the Ser 51 acceptor site in eIF2alpha , its mode of binding to PKR affords the Ser 51 site full access to the catalytic cleft of PKR . ^^^ The generality and implications of the structural mechanisms uncovered for PKR to the larger family of four human eIF2alpha protein kinases are discussed . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The antiviral RNA dependent protein kinase , PKR , binds to viral double stranded RNA in the cell and halts protein synthesis by phosphorylating the alpha subunit of the translation initiation factor eIF 2 . ^^^ PKR and eIF2alpha : integration of kinase dimerization , activation , and substrate docking . ^^^ In this issue of Cell , two complementary papers Dar et al . ( 2005 ) and Dey et al . ( 2005 ) address the interaction between PKR and eIF2alpha . ^^^ The structures of eIF2alpha bound to PKR reveal that PKR forms a dimer , the interface of which is essential for kinase activation , and demonstrate how this protein substrate docks to its kinase . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Infection with cp BVDV was found to induce PKR activation , eIF2alpha phosphorylation , translation inhibition and NF kappaB activation . ^^^ In contrast , PKR activity and eIF2alpha phosphorylation were not induced during infection with the ncp BVDV . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Concordantly , a direct substrate of PKR , the alpha subunit of eukaryotic initiation factor 2 ( eIF 2alpha ) , was equally phosphorylated in EBV positive and EBV negative cells following interferon treatment . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Serine / threonine RNA dependent protein kinase ( PKR ) is an eIF2alpha kinase family member induced by type 1 IFN and activated in response to dsRNA or virus infection . ^^^ Site specific tyrosine phosphorylation is essential for efficient dsRNA binding , dimerization , kinase activation and eIF2alpha phosphorylation of PKR . ^^^ Our data demonstrate an important role of tyrosine phosphorylation in biochemical and biological processes caused or mediated by the activation of the eIF2alpha kinase PKR . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Infection with these same strains decreased transcript and protein levels of P 58 ( IPK ) , the cellular inhibitor of the eukaryotic initiation factor 2alpha ( eIF2alpha ) kinases PKR and PERK . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Unlike wild type PKR , the variant protein named PKR DE 12 is incapable of auto phosphorylation and phosphorylation of eIF 2 a , indicating that the kinase sub domains 3 and 4 embedded in exon 12 are indispensable for catalytic function . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Upon activation by viral infection or dsRNA , PKR phosphorylates its substrate , the alpha subunit of eukaryotic translation initiation factor 2 ( eIF2alpha ) leading to inhibition of translation initiation . ^^^ We have demonstrated that exposure to ethanol increased the phosphorylation of PKR and eIF2alpha in the developing cerebellum . ^^^ The effect of ethanol on PKR / eIF2alpha phosphorylation positively correlated to the expression of PACT / RAX in cultured neuronal cells . ^^^ Using PKR inhibitors and PKR null mouse fibroblasts , we verified that ethanol induced eIF2alpha phosphorylation was mediated by PKR . ^^^ Overexpression of a wild type RAX dramatically enhanced sensitivity to ethanol induced PKR / eIF2alpha phosphorylation , as well as translational inhibition and cell death . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Upon binding double stranded RNA ( dsRNA ) , PKR can become activated and phosphorylate cellular targets , such as eukaryotic translation initiation factor 2alpha ( eIF 2alpha ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In mammals , four different protein kinases , heme regulated inhibitor , double stranded RNA dependent protein kinase ( PKR ) , general control non derepressible 2 ( GCN 2 ) and PKR like endoplasmic reticulum kinase , regulate protein synthesis in response to environmental stresses by phosphorylating the alpha subunit of the initiation factor 2 ( eIF2alpha ) . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Activated PKR phosphorylates the translation initiation factor eIF 2 , thereby inhibiting viral and cellular protein synthesis and virus replication . ^^^ First , we showed that an NS1A protein lacking RNA binding activity , like the wild type ( wt ) protein , blocked PKR activation by PACT in vivo , as well as the downstream effects of PKR activation in cells , namely , eIF 2 phosphorylation and apoptosis . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
We show in the present study that one eIF2alpha kinase family member , PKR ( double stranded RNA dependent protein kinase ) , is activated in the cortex and hippocampus at 30 min of SE , reflecting the levels of eIF2alpha ( P ) in these areas . ^^^ In PKR deficient animals subjected to SE , eIF2alpha phosphorylation was clearly evident coincident with activation of a secondary eIF2alpha kinase , PEK / PERK ( pancreatic eIF2alpha kinase / RNA dependent protein kinase like endoplasmic reticulum kinase ) , denoting a compensatory mechanism between the two kinases . ^^^ These results taken together suggest that PKR mediated phosphorylation of eIF2alpha contributes to inhibition of protein synthesis in the brain during SE and that sustained high levels of eIF2alpha phosphorylation may facilitate ensuing cell death in the most affected areas of the brain in TLE . . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Thus , knock down of RAX expression by 80 % using small interfering RNA ( siRNA ) prevents IFNgamma / tumor necrosis factor alpha ( TNFalpha ) induced PKR activation and eIF2alpha phosphorylation , IkappaB degradation , IRF 1 expression , and STAT 1 phosphorylation , resulting in enhanced murine embryonic fibroblast ( MEF ) cell survival . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
The interferon induced dsRNA activated protein kinase ( PRKR ) belongs to a subclass of serine / threonine kinases , involved in the regulation of protein synthesis by phosphorylation of the alpha subunit of initiation factor eIF 2 . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
In response to various cellular stress , eIF2alpha is phosphorylated by distinct protein kinases ( PKR , PERK , GCN 2 , and HRI ) , and this event results in protein translation shut down . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
PKR belongs to a family of kinases that phosphorylate the eukaryotic translation initiation factor 2 alpha ( eIF2alpha ) and activate common downstream signaling pathways . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
TNFalpha treatment induced eIF2alpha phosphorylation and activation of caspase 3 primarily through the dsRNA activated eIF2alpha kinase PKR . ^^^ The proapoptotic effects of PKR mediated eIF2alpha phosphorylation contrast with the anti apoptotic response upon activation of the PKR related endoplasmic reticulum eIF2alpha kinase , PERK . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Sustained translation in HSV 1 infected cells exposed to acute ER stress does not involve the interferon induced , double stranded RNA responsive eIF2alpha kinase PKR , and it does not require either the PKR inhibitor encoded by the Us 11 gene or the eIF2alpha phosphatase component specified by the gamma ( 1 ) 34 . 5 gene , the two viral functions known to regulate eIF2alpha phosphorylation . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
Previously , ICP34 . 5 was demonstrated to have a crucial role in evading the innate immune response to infection by mediating the dephosphorylation of eIF2alpha , a translation initiation factor phosphorylated by PKR during the antiviral response . ^^^ Our study revealed that cells responded to infection within 3 h through PKR dependent eIF2alpha phosphorylation and that the majority of up regulated genes at 3 h postinfection were involved in the antiviral response . ^^^
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P19525 and P05198	Pubmed	SVM Score :0.0
NA