Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.69700578
The ability of WG 10 eIF 2 to exchange guanine nucleotides independent of an eIF2B like protein and the inability of phosphorylated WG 10 eIF 2 to interact with reticulocyte eIF2B suggests that WG 10 eIF 2 is different from mammalian eIF 2 and these differences may have occurred in evolution probably due to some changes in the amino acid sequences around the phosphorylation site in eIF2alpha . . 0.69700578^^^ Unlike reticulocyte eIF 2 ( alphaP ) , phosphorylated WG 10 eIF 2 is unable to interact with reticulocyte eIF2B to form a 15S complex . 0.67408763^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.57926306
The altered phosphatase specificity upon association of eIF 2 with eIF 2B also affects the access of protein kinases to these phosphorylation sites . 0.57926306^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.5353903
In addition , the association of eIF 2B with intact eIF 2 , but not with eIF 2 ( alpha gamma ) , reduces by two fold the rate and extent of removal of 32P by alkaline phosphatase from CK 2 phosphorylated 82 kDa subunit . . 0.5353903^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
There were no reproducible , significant changes in eIF 4A , eIF 4B , or eIF 2 beta in cells infected by any of these viruses . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The gene encoding eIF 2 beta in S . cerevisiae maps to chromosome 16 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The guanine nucleotide exchange factor eIF2B mediates the exchange of GDP bound to translation initiation factor eIF 2 for GTP . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We also show that NF 90 , NF 45 , and eIF 2 beta are substrates for DNA PK in vitro . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Analysis showed that after caspase cleavage , exchange of GDP bound to eIF 2 was very rapid and no longer dependent upon eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of eIF2alpha was inversely related to eIF2B activity under all conditions . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Since BDNF and insulin increased the activity of eIF2B and eIF 2 , the only difference between them was eIF4E phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Inhibition of acinar protein synthesis can be mediated by inhibition of eIF2B following phosphorylation of eIF2alpha . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The mutations in eIF2B did not affect the interaction with eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Ischemia and reperfusion also resulted in increased phosphorylation of eIF 2 and eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Interactions of the heme regulated eIF 2 alpha kinase with heat shock proteins in rabbit reticulocyte lysates . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Vaccinia virus encoded eIF 2 alpha homolog abrogates the antiviral effect of interferon . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Two phosphorylation sites on eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Purification of a novel eIF 2 alpha protein kinase from calf brain . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The mechanism of inhibition of GEF function by eIF 2 alpha phosphorylation has also been investigated . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Association of the heme controlled eIF 2 alpha kinase with spectrin derived peptides . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The phosphorylation of eIF 2 alpha inhibits polypeptide chain initiation by preventing dissociation of eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Histidinol did not stimulate the activity of the endogenous kinase for eIF 2 alpha subunit in extracts prepared from HeLa cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Characterization of purified double stranded RNA activated eIF 2 alpha kinase from rabbit reticulocytes . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
However , neither IFN alpha A nor IFN gamma induced the phosphorylation of P 1 and eIF 2 alpha in GM2767A cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The complex contains no unphosphorylated eIF 2 alpha , and the GDP present is freely dissociable . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Addition of hemin to lysates prevents activation of the eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Activated PKR inhibits protein synthesis by phosphorylating initiation factor eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Regulation of the interferon inducible eIF 2 alpha protein kinase by small RNAs . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
These results strongly support the hypothesis that mammalian eIF 2 alpha and GCN 3 are homologues . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Regulation of heme regulated eIF 2 alpha kinase and its expression in erythroid cells . ^^^
Interacting proteins: P20042 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: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
The eIF 2 alpha protein kinases , regulators of translation in eukaryotes from yeasts to humans . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Using GCN 4 as a reporter of eIF 2 alpha phosphorylation and translational regulation in yeast . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Analysis of eIF 2 alpha kinases in yeast . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
RNA binding proteins TIA 1 and TIAR link the phosphorylation of eIF 2 alpha to the assembly of mammalian stress granules . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor 2 ( eIF 2 ) associated glycoprotein p 67 protects eIF2alpha phosphorylation from kinases . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Stress induced apoptosis in Spodoptera frugiperda ( Sf 9 ) cells : baculovirus p 35 mitigates eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Interdomain interactions regulate the activation of the heme regulated eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Sensory denervation modulates eIF 2 alpha kinase expression in the rabbit lacrimal gland . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The ICF activity appeared to copurify with a complex of initiation factors eIF 2 and eIF 2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
First , the mutant ' s translational defect can be relieved by addition of eIF 2 or eIF 2B ( GTP recycling factor ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Protein synthesis in the developing rat liver : participation of initiation factors eIF 2 and eIF 2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Addition of eIF 2 and of eIF 2B changed the selection process for both types of RNA . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The p 38 subunit of wheat eIF 2 is therefore the equivalent of mammalian eIF2beta . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The majority of the known GCD genes encode subunits of the general translation initiation factor eIF 2 or eIF 2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
DNA sequence analysis of these alleles and of eIF 2 beta suppressor alleles isolated from haploid strains , identified point mutations that altered one of six amino acids that map to a Cys X 2 Cys X 19 Cys X 2 Cys `` zinc finger ' ' motif and immediately adjacent residues . ^^^ Five of the affected amino acids are identical in the human and yeast eIF 2 beta protein . ^^^ Together with earlier studies ( Donahue et al . , 1988 ) , these point mutations implicate the zinc finger domain of eIF 2 beta in start site selection during the scanning process . ^^^ Our studies indicate that the cysteine residues and the intervening amino acids of this motif are essential for eIF 2 beta function in translation initiation in vivo . ^^^ However , the effects observed in cells containing a copy of eIF 2 beta with a deletion of this motif suggest that this mutated form is still able to associate with other components of the initiation complex , imparting defects on translation initiation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This inhibition is relieved upon addition of ATP , showing that Cibacron blue 3G A competes with ATP for eIF 2 . eIF 2 beta subunit , active in binding of mRNA , is recovered upon chromatography of eIF 2 in denaturing conditions over matrix bound Cibacron blue 3G A . ^^^ During initiation of protein synthesis , the eIF 2 beta subunit may thus interact with three ligands important for translational control : Met tRNA ( f ) , mRNA and ATP . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
None of the sua genes is allelic to SUI 2 or sui 3 , which encode eIF 2 alpha and eIF 2 beta , respectively , or to SUI 1 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
When physiological substrates for casein kinase 2 are examined , glycogen synthase and eukaryotic initiation factor 3 ( eIF 3 ) ( p 120 ) are phosphorylated by the alpha subunit at a rate equivalent to that of the holoenzyme , while phosphorylation of eIF 3 ( p 67 ) is reduced 9 fold and eIF 2 beta is not modified . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have now applied the same method in combination with CNBr cleavage and microsequence analysis in order investigate which part of the polypeptide chain of eIF 2 beta is in close contact to the bound GTP . ^^^ From the three main CNBr fragments of eIF 2 beta , the C terminal one was found to be labelled by the applied GTP photoaffinity analogue , Guo ( 2 ' , 3 ' TDBH ) ppp . ^^^ Because the cDNA sequence of the gamma subunit of eIF 2 has not yet been published and because cDNA sequence analysis of eIF 2 beta revealed only two out of three consensus sequence elements of a GTP binding domain , we also sequenced the CNBr fragments of eIF 2 gamma . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Quaternary complexes were fixed with glutaraldehyde and reacted with affinity purified polyclonal antibodies against eIF 2 alpha , eIF 2 beta or eIF 2 gamma . ^^^ Within this region , eIF 2 alpha points to the rear side , whereas eIF 2 beta and eIF 2 gamma point to the frontal side of the 40S subunit indicating an elongated shape of eIF 2 about 15 nm long . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The 1416 bp cDNA encodes a protein of 333 amino acids ( 38 , 404 daltons ) with characteristics that resemble authentic purified eIF 2 beta . ^^^ De novo synthesized eIF 2 beta from cDNA transcripts incorporates into endogenous rabbit eIF 2 complexes . ^^^ The polylysine blocks and the zinc finger motif suggest that eIF 2 beta interacts with RNA . ^^^ A yeast protein , Sui 3 , isolated as an extragenic suppressor of his 4 initiation codon mutations , exhibits extensive sequence identity with human eIF 2 beta , especially in the polylysine and zinc finger domains , thereby reinforcing the view that these elements are important for function . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Mutations at a Zn ( 2 ) finger motif in the yeast eIF 2 beta gene alter ribosomal start site selection during the scanning process . ^^^ This motif is present in a cDNA sequence encoding the human eIF 2 beta gene product . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
These two forms of eIF 2 beta polypeptides are also detected in reticulocyte lysates when the proteins are resolved by two dimensional isoelectric focusing dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblotting . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation by these kinases is additive , suggesting that they phosphorylate different sites ( serine residues ) in eIF 2 beta . ^^^ Two dimensional peptide mapping of the phosphopeptides generated from labelled eIF 2 beta by digestion with trypsin , cyanogen bromide or Staphylococcus aureus V 8 proteinase showed that protein kinase C and casein kinase 2 phosphorylated distinct and different sites in this protein . ^^^ Analysis of the phosphopeptides derived from eIF 2 beta labelled by both kinases together strongly suggested that the sites labelled by protein kinase C and casein kinase 2 are adjacent in the primary sequence . ^^^ Rat liver eIF 2 beta was also found to be a substrate for protein kinase C and casein kinase 2 , which were again shown to label different serine residues . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
These data show that the DEAE 100 inhibitor ( s ) contains a nuclease while the DEAE 350 inhibitor ( s ) is associated with eIF 2 alpha and eIF 2 beta protein kinases . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
One of these contained all three components ( eIF 2 alpha , eIF 2 beta , eIF 2 gamma ) characteristic of mammalian eIF 2 , whilst the other fraction contained only two . ^^^ The absence of eIF 2 beta from this fraction was not due to its proteolytic degradation during purification since it was unaffected by the inclusion of a range of proteinase inhibitors in the isolation media . ^^^ The properties of eIF 2 containing or lacking eIF 2 beta have been directly compared . ^^^ It was found that eIF 2 beta was not required for the binding of guanine nucleotides to eIF 2 or for formation of ternary initiation complexes with GTP and the initiator tRNA . eIF 2 lacking eIF 2 beta was able to form 40 S initiation complexes and the presence of eIF 2 beta was also unnecessary for the stimulation of eIF 2 activity by the recycling factor , eIF 2B . ^^^ Some of these findings are at variance with previous reports in which eIF 2 beta was removed proteolytically . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In contrast , the beta subunits of the liver and reticulocyte factors were distinct ; they had different molecular weights , and antibodies against rat liver eIF 2 beta did not recognize the beta subunit of the reticulocyte factor . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor ( eIF ) 2 alpha , eIF 2 beta , and eIF 4A each formed a single immunoreactive spot ; eIF 2 gamma formed 2 spots ; and eIF 4B formed a complex array of 12 20 spots . ^^^ After 4 days of growth in unreplenished medium , when translation rates have dropped 4 6 fold , several alterations in the isoelectric forms were observed : eIF 2 alpha now occurred in 2 forms , eIF 2 beta was present in 3 4 forms , and the most acidic cluster of eIF 4B variants was decreased or absent while a new isoelectric variant appeared at the basic end of the array . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
On the basis of immunoblotting techniques , eIF 4A is highly conserved , eIF 2 alpha , eIF 3 , and eIF 4B are somewhat less conserved , and eIF 2 beta is the least conserved of the proteins examined . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Immunoblot analyses show that eIF 2 alpha and eIF 2 beta become modified during heat shock , and eIF 4B variants disappear . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Spots identified as eukaryotic initiation factor ( eIF ) 2 alpha , eIF 2 beta , eIF 2 gamma , eIF 4A , and four eIF 3 proteins of less than 50 , 000 Da corresponded to moderately abundant lysate proteins . ^^^ Minor isoelectric variant forms of eIF 2 beta , eIF 2 gamma , and eIF 4A were detected by immunoblot analysis of lysate proteins , suggesting either covalent modification of these factor proteins or contaminating antibodies . eIF 2 beta and eIF 4B were present in at least two isoelectric forms , confirming covalent modification of these proteins . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Cross linking of Met tRNAf to eIF 2 beta and to the ribosomal proteins S3a and S 6 within the eukaryotic inhibition complex , eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The latter result indicates that the gamma subunit of eIF 2 participates in recognition of the start site for protein synthesis , a role previously demonstrated in yeast for eIF 2 alpha and eIF 2 beta . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Here we identify the sites at which eIF 2 beta is phosphorylated in vitro by three well characterised protein kinases , casein kinase 2 ( which phosphorylates serine residues 2 and 67 ) , protein kinase C ( serine 13 ) and cAMP dependent protein kinase ( serine 218 ) . ^^^ This constitutes an essential prerequisite for studying the phosphorylation of eIF 2 beta in vivo . ^^^ The major kinase activity against eIF 2 beta in reticulocyte lysates appears in CK 2 and protein phosphatase 2A is the principal enzyme responsible for dephosphorylation of eIF 2 beta phosphorylated by this kinase . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
SRD 1 encodes a putative 225 amino acid , 26 kDa protein containing a C2 / C2 zinc finger motif that is also found in some transcription regulators and the eIF 2 beta translation initiating factors . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Isolation and characterization of the Drosophila melanogaster gene encoding translation initiation factor eIF 2 beta . ^^^ The aa sequence comparison of D . melanogaster eIF 2 beta with its human and yeast counterparts demonstrates a high degree of similarity , especially within the C terminal region . ^^^ Northern analysis indicates quasi constitutive expression of eIF 2 beta throughout D . melanogaster development . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Rabbit eIF 2 beta transcripts were then specifically amplified by PCR and sequenced . ^^^ Comparison of the deduced amino acid sequence with that of human eIF 2 beta reveals a very high degree of sequence identity . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have identified the GCD 11 gene product as the gamma subunit of eIF 2 by the following criteria : ( 1 ) sequence identities with mammalian eIF 2 gamma peptides ; ( 2 ) increased eIF 2 activity in extracts prepared from cells cooverexpressing GCD 11 , eIF 2 alpha , and eIF 2 beta ; and ( 3 ) cross reactivity of antibodies directed against the GCD 11 protein with the 58 kDa polypeptide present in purified yeast eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Analysis of polysome profiles and determination of both eukaryotic initiation factor 2 ( eIF 2 ) activity and amount of eIF 2 beta protein in the liver of fetal and 1 h old neonatal rats , indicate a rapid activation of translation initiation without changes in the amount of the translational machinery available between both stages of liver development . ^^^ Appearance of a more acidic eIF 2 beta subunit form in two dimensional Western blots from 1 h old rat livers suggests that covalently regulated modifications of the initiation factor phosphoproteins might be responsible for increased translation in the neonatal liver . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Similar to the increase in ribosomes and mRNA , the number of eIF 2 alpha , eIF 2 beta , and eIF 4 alpha molecules per cell also increase 2 3 fold . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A difference in the rate of ribosomal elongation balances the synthesis of eukaryotic translation initiation factor ( eIF ) 2 alpha and eIF 2 beta . ^^^ Northern analysis of K 562 cell mRNA revealed that eIF 2 beta was five times more abundant than eIF 2 alpha . ^^^ Addition of equal amounts of synthetic capped mRNA for eIF 2 alpha and eIF 2 beta to an in vitro translation reaction produced five times more eIF 2 alpha protein than eIF 2 beta . ^^^ Determination of the polysome profile for alpha and beta mRNA in K 562 cells indicated eIF 2 alpha was translated more efficiently than eIF 2 beta . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Among them are six known sequences coding for : acid sphingomyelinase , fibronectin , SPARC , nm 23 metastasis suppressor protein , and two translation factors , eIF 2 beta and EF 1 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The isoelectric forms of the beta subunit of eIF 2 factor , eIF 2 beta , were different in the diabetic and the control animals , indicating that insulin deficiency modifies the phosphorylation of specific substrates . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Identification of a regulatory subcomplex in the guanine nucleotide exchange factor eIF2B that mediates inhibition by phosphorylated eIF 2 . ^^^ Eukaryotic translation initiation factor 2B ( eIF2B ) is a five subunit complex that catalyzes guanine nucleotide exchange on eIF 2 . ^^^ Phosphorylation of the alpha subunit of eIF 2 [ creating eIF 2 ( alphaP ] ) converts eIF 2 10 GDP from a substrate to an inhibitor of eIF2B . ^^^ We showed previously that the inhibitory effect of eIF 2 ( alphaP ) can be decreased by deletion of the eIF2B alpha subunit ( encoded by GCN 3 ) and by point mutations in the beta and delta subunits of eIF2B ( encoded by GCD 7 and GCD 2 , respectively ) . ^^^ These findings , plus sequence similarities among GCD 2 , GCD 7 , and GCN 3 , led us to propose that these proteins comprise a regulatory domain that interacts with eIF 2 ( alphaP ) and mediates the inhibition of eIF2B activity . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Homologous segments in three subunits of the guanine nucleotide exchange factor eIF2B mediate translational regulation by phosphorylation of eIF 2 . eIF2B is a five subunit guanine nucleotide exchange factor that is negatively regulated by phosphorylation of the alpha subunit of its substrate , eIF 2 , leading to inhibition of translation initiation . ^^^ To analyze this regulatory mechanism , we have characterized 29 novel mutations in the homologous eIF2B subunits encoded by GCD 2 , GCD 7 , and GCN 3 that reduce or abolish inhibition of eIF2B activity by eIF 2 phosphorylated on its alpha subunit [ eIF 2 ( alphaP ) ] . ^^^ Most , if not all , of the mutations decrease sensitivity to eIF 2 ( alphaP ) without excluding GCN 3 , the nonessential subunit , from eIF2B ; thus , all three proteins are critical for regulation of eIF2B by eIF 2 ( alphaP ) . ^^^ We propose that these segments form a single domain in eIF2B that makes multiple contacts with the alpha subunit of eIF 2 , around the phosphorylation site , allowing eIF2B to detect and respond to phosphoserine at residue 51 . ^^^ Most of the eIF 2 is phosphorylated in certain mutants , suggesting that these substitutions allow eIF2B to accept phosphorylated eIF 2 as a substrate for nucleotide exchange . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Fasting and refeeding caused alterations in translation initiation in both skeletal muscle and liver that were not associated with any detectable changes in the activity of eIF2B or in the phosphorylation state of eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor 2B ( eIF2B ) is a guanine nucleotide exchange factor which mediates the exchange of GDP ( bound to initiation factor eIF 2 ) for GTP , thus regenerating the active [ eIF2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This suggestion is also consistent with the findings that vanadium compounds do not stimulate phosphorylation of the alpha ( alpha ) subunit of initiation factor 2 ( eIF 2 ) or decrease the guanine nucleotide exchange activity of eIF2B , which is required to exchange GDP for GTP in eIF2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Identification of interprotein interactions between the subunits of eukaryotic initiation factors eIF 2 and eIF2B . ^^^ Specifically , regulation of the interaction of eIF 2 with the guanine nucleotide exchange factor , eIF2B , is a key mechanism for controlling translation under a variety of conditions . ^^^ Phosphorylation of the alpha subunit of eIF 2 converts the protein into a competitive inhibitor of eIF2B by causing an increase in the binding affinity of eIF2B for eIF 2 . ^^^ Consequently , it has been assumed that the alpha subunit of eIF 2 is directly involved in binding to eIF2B . ^^^ In the present study , eIF 2 was found to bind only to the delta and epsilon subunits of eIF2B , and eIF2B was shown to bind only to the beta subunit of eIF 2 by far Western blot analysis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have used an in vitro nucleotide exchange assay to show that wild type yeast eIF2B is inhibited by phosphorylated eIF 2 [ eIF 2 ( alphaP ) ] and to characterize eIF2B regulatory mutations that render translation initiation insensitive to eIF 2 phosphorylation in vivo . ^^^ Unlike wild type eIF2B , eIF2B complexes with mutated GCN 3 or GCD 7 subunits efficiently catalyzed GDP exchange using eIF 2 ( alphaP ) as a substrate . ^^^ Using an affinity binding assay , we show that an eIF2B subcomplex of the GCN 3 , GCD 7 , and GCD 2 subunits binds to eIF 2 and has a higher affinity for eIF 2 ( alphaP ) , but it lacks nucleotide exchange activity . ^^^ In contrast , the GCD 1 and GCD 6 subunits form an eIF2B subcomplex that binds equally to eIF 2 and eIF 2 ( alphaP ) . ^^^ Remarkably , this second subcomplex has higher nucleotide exchange activity than wild type eIF2B that is not inhibited by eIF 2 ( alphaP ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The alpha subunit of eukaryotic initiation factor eIF 2 ( eIF2alpha ) plays an important role in the regulation of mRNA translation through modulation of the interaction of eIF 2 and a second initiation factor , eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Both the five and four subunit forms of eIF2B exhibit similar rates of guanine nucleotide exchange activity using unphosphorylated eIF 2 as substrate . ^^^ In contrast , eIF2B lacking the alpha subunit is insensitive to inhibition by eIF 2 ( alphaP ) and is able to exchange guanine nucleotide using eIF 2 ( alphaP ) as substrate at a faster rate compared with five subunit eIF2B . ^^^ Finally , a double point mutation in the delta subunit of eIF2B has been identified that results in insensitivity to inhibition by eIF 2 ( alphaP ) and exhibits little exchange activity when eIF 2 ( alphaP ) is used as substrate . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor eIF2B plays a key role in the regulation of protein synthesis through its ability to catalyze the exchange of GDP bound to a second initiation factor , eIF 2 , for free GTP . ^^^ The purified five subunit eIF2B complex had high GEF activity as assayed by using [ 3H ] GDP bound to eIF 2 as a substrate . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
At mild heat shock temperatures the main cause for inhibition is the inactivation of the guanine nucleotide exchange factor eukaryotic initiation factor 2B ( eIF2B ) ; under more severe heat shock conditions the activity of several initiation factors is compromised . eIF2B is required for GDP / GTP exchange on eIF 2 , which delivers methionyl tRNA to the 40 S ribosomal subunit . ^^^ In agreement with observations in cells exposed to mild heat shocks , the thermal inactivation of eIF2B could be ascribed to neither eIF2alpha phosphorylation nor the induction of another inhibitor . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The changes in eIF2B activity could be explained in part by modulation of the phosphorylation state of the alpha subunit of eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Our findings show that Rps 31 deficient ribosomes are altered in a way that decreases the eIF2B requirement and that the small ribosomal subunit mediates the effects of low eIF2B activity on cell viability and translational regulation in response to eIF 2 phosphorylation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In the initiation phase of eukaryotic translation , eIF 5 stimulates the hydrolysis of GTP bound to eIF 2 in the 40S ribosomal pre initiation complex , and the resultant GDP on eIF 2 is replaced with GTP by the complex nucleotide exchange factor , eIF2B . ^^^ We also find that three lysine rich boxes in the N terminal segment of eIF2beta mediate the binding of eIF 2 to both eIF 5 and eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The exchange of GDP bound to eIF 2 for GTP is a prerequisite to binding Met tRNAi and is mediated by a second initiation factor , eIF2B . ^^^ In what is probably the best characterized mechanism for the regulation of mRNA translation , phosphorylation of eIF 2 on its smallest , or alpha , subunit converts eIF 2 from a substrate of eIF2B into a competitive inhibitor . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of Ser ( 51 ) on the alpha subunit of eIF 2 [ eIF2alpha ( P ) ] generates a competitive inhibitor of eIF2B , thereby preventing the replenishment of GTP onto eIF 2 , thus blocking translation initiation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Serine 48 in initiation factor 2 alpha ( eIF 2 alpha ) is required for high affinity interaction between eIF 2 alpha ( P ) and eIF2B . ^^^ Phosphorylation of the serine 51 residue in the alpha subunit of translational initiation factor 2 in eukaryotes ( eIF 2 alpha ) impairs protein synthesis presumably by sequestering eIF2B , a rate limiting pentameric guanine nucleotide exchange protein which catalyzes the exchange of GTP for GDP in the eIF 2 GDP binary complex . ^^^ To further understand the importance of eIF 2 alpha phosphorylation in the interaction between eIF 2 alpha ( P ) and eIF2B proteins and thereby the regulation of eIF2B activity , we expressed the wild type ( wt ) and a mutant eIF 2 alpha in which the serine 48 residue was replaced with alanine ( 48A mutant ) in the baculovirus system . ^^^ Furthermore , the extents of inhibition of eIF2B activity and formation of the eIF 2 alpha ( P ) eIF2B complex that occurs due to eIF 2 alpha phosphorylation in poly ( IC ) treated rabbit reticulocyte lysates were decreased significantly in the presence of insect cell extracts expressing the 48A mutant eIF 2 alpha compared to those for wt . ^^^ These findings support the hypothesis that the serine 48 residue is required for high affinity interaction between eIF 2 alpha ( P ) and eIF2B . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The effects of nutrients on the activation of eIF2B do not reflect changes in the phosphorylation of eIF 2 ( and , by inference , operation of a kinase analogous to yeast Gcn2p ) , or a requirement for nutrients for inactivation of glycogen synthase kinase 3 or dephosphorylation of eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Moreover , the guanine nucleotide exchange activity of eIF2B was unaffected as was phosphorylation of the alpha subunit of eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In contrast , no differences in the phosphorylation state of eIF2alpha or the activity of eIF2B were noted among treatment groups . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Here we provide a comparative sequence analysis of the beta subunit of eIF 2 and its archaeal counterpart ( aIF2beta ) . aIF2beta differs from eIF2beta in not possessing an N terminal extension implicated in binding RNA , eIF 5 and eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Hepatic eIF2B activity was decreased 24 % in alcohol treated rats , and this was associated with a 95 % increase in eIF2alpha phosphorylation . ^^^ In contrast to liver , neither eIF2B activity nor the phosphorylation of eIF2alpha was affected in muscle of alcohol treated rats . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic translation initiation factor 2B ( eIF2B ) is the guanine nucleotide exchange factor for protein synthesis initiation factor 2 ( eIF 2 ) . ^^^ We have analyzed the roles of different regions of eIF2Bepsilon in catalysis , in eIF2B complex formation , and in binding to eIF 2 by characterizing mutations in the Saccharomyces cerevisiae gene encoding eIF2Bepsilon ( GCD 6 ) that impair the essential function of eIF2B . ^^^ Finally , missense mutations identified within this region do not affect the catalytic activity of eIF2Bepsilon alone or its interactions with the other eIF2B subunits or with eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The content of eIF2alpha or the amount of eIF2alpha in the phosphorylated form did not change in response to LPS . eIF2B activity was decreased in muscle 4 h post LPS but activity returned to control values by 24 h . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic translation initiation factor 2B ( eIF2B ) is the heteropentameric guanine nucleotide exchange factor for translation initiation factor 2 ( eIF 2 ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
These findings suggest that plant eIF2alpha is capable of interacting with the guanine nucleotide exchange factor eIF2B within the context of the eIF 2 holoenzyme and provide direct evidence for its ability to participate in phosphorylation mediated translational control in vivo . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic translation initiation factor , eIF2B , is a guanine nucleotide exchange factor ( GEF ) composed of five dissimilar subunits . eIF2B is important for regenerating GTP bound eIF 2 during the initiation process . ^^^ Removal of the C terminal 552 amino acids of eIF2B epsilon markedly reduced its interaction with the beta subunit of eIF 2 whereas loss of the N terminal 431 amino acids did not . ^^^ In contrast , the C terminal domain of eIF2B epsilon is sufficient alone for binding the beta subunit of its substrate , eIF 2 , in vitro . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Protein synthesis is not inhibited by the high eIF2alpha phosphorylation in carcinoma cells , probably because they contain higher levels of eIF2B , the initiation factor that is inhibited by eIF2alpha phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of serine 51 in initiation factor 2 alpha ( eIF 2 alpha ) promotes complex formation between eIF 2 alpha ( P ) and eIF2B and causes inhibition in the guanine nucleotide exchange activity of eIF2B . ^^^ Inhibition of the GNE activity of eIF2B leads to impairment in eIF 2 recycling and protein synthesis . ^^^ Analysis of these mutants has provided novel insight into the role of 51 serine in the interaction between eIF 2 and eIF2B . ^^^ Our results show that the increased interaction between eIF 2 and eIF2B protein , occurring in reticulocyte lysates due to increased eIF2alpha phosphorylation , is decreased significantly by the addition of mutant 51A protein but not 51D . ^^^ Phosphorylation of serine 51 residue on the alpha subunit of eukaryotic initiation factor 2 ( eIF2alpha ) inhibits the guanine nucleotide exchange ( GNE ) activity of eIF2B , presumably , by forming a tight complex with eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The alpha subunit of eIF 2 plays a critical role in regulating nucleotide exchange via phosphorylation at serine 51 , which converts eIF 2 into a competitive inhibitor of the eIF2B catalyzed exchange reaction . ^^^ These data indicate that eIF2alpha is required for structural interactions between eIF 2 and eIF2B that promote wild type rates of nucleotide exchange . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Acute alcohol intoxication did not significantly alter the myocardial content of eIF 2 alpha or eIF2B epsilon , the extent of eIF 2 alpha phosphorylation , or the activity of eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor ( eIF ) 2B catalyzes a key regulatory step in the initiation of mRNA translation . eIF2B is well characterized in mammals and in yeast , although little is known about it in other eukaryotes . eIF2B is a hetropentamer which mediates the exchange of GDP for GTP on eIF 2 . ^^^ Extracts of D . melanogaster S 2 Schneider cells display eIF2B activity , which is inhibited by phosphorylation of eIF2alpha , showing the insect factor is regulated similarly to eIF2B from other species . ^^^ In S 2 cells , serum starvation increases eIF2alpha phosphorylation , which correlates with inhibition of eIF2B , and both effects are reversed by serum treatment . ^^^ This shows that eIF2alpha phosphorylation and eIF2B activity are under dynamic regulation by serum . eIF2alpha phosphorylation is also increased by endoplasmic reticulum stress in S 2 cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In this work , we show that , in addition to the eIF 2 beta binding region at the C terminus of eIF 5 , the N terminal region of eIF 5 is also required for eIF 5 dependent GTP hydrolysis . ^^^ Mutation of this arginine residue to alanine or even to conservative lysine caused a severe defect in the ability of eIF 5 to promote GTP hydrolysis from the 40 S initiation complex , although the ability of these mutant proteins to bind to eIF 2 beta remained unchanged . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The association between plant eIF2alpha and yeast eIF2B is supported by their specific coimmunoprecipitation from transgenic yeast cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of eIF2alpha converts the factor from a substrate into a competitive inhibitor of the guanine nucleotide exchange factor , eIF2B , leading to a decline in mRNA translation . ^^^ Furthermore , the reduction in eIF2B activity is associated with enhanced phosphorylation of eIF2alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic translation initiation factor 2 ( eIF 2 ) is a G protein heterotrimer required for GTP dependent delivery of initiator tRNA to the ribosome . eIF2B , the nucleotide exchange factor for eIF 2 , is a heteropentamer that , in yeast , is encoded by four essential genes and one nonessential gene . ^^^ We found that increased levels of wild type eIF 2 , in the presence of sufficient levels of initiator tRNA , overcome the requirement for eIF2B in vivo . ^^^ The effects described are further enhanced in the presence of a mutation in the G protein ( gamma ) subunit of eIF 2 , gcd 11 K250R , which mimics the function of eIF2B in vitro . ^^^ Our results suggest that the eIF2betagamma complex is capable of carrying out the essential function ( s ) of eIF 2 in the absence of eIF2alpha and eIF2B and are consistent with the idea that the latter function primarily to regulate the level of eIF2 . ^^^ Consistent with bypassing eIF2B , these conditions also suppress the lethal effect of overexpressing the mammalian tumor suppressor PKR , an eIF2alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Increased phosphorylation of the alpha subunit of eIF 2 ( eIF 2 alpha ) and eIF2B inhibition paralleled the inhibition of translation in the hippocampus , but they normalized to control values , including the CA 1 subfield , after 4 6 h of reperfusion . eIF4E and 4E BP 1 were significantly dephosphorylated during ischaemia and total eIF4E levels decreased during reperfusion both in the cortex and hippocampus , with values normalizing after 4 h of reperfusion only in the cortex . ^^^ Our findings are consistent with a potential role for eIF4E , 4E BP 1 and eIF4G in the down regulation of translation during ischaemia . eIF 2 alpha , eIF2B , eIF4G and p 70 ( S6K ) are positively implicated in the translational inhibition induced at early reperfusion , whereas eIF4F complex formation is likely to contribute to the persistent inhibition of translation observed at longer reperfusion times . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
They lie at the extreme C terminus and are required for the interaction of eIF2Bepsilon with its substrate , eIF 2 , in vivo and for eIF2B activity in vitro . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylated eIF 2 acts as a dominant inhibitor of the guanine nucleotide exchange factor eIF2B and prevents the recycling of eIF 2 between successive rounds of protein synthesis . ^^^ Extensive phosphorylation of eIF 2 alpha and strong inhibition of eIF2B activity can result in the downregulation of the overall rate of protein synthesis ; less marked changes may lead to alterations in the selective translation of alternative open reading frames in polycistronic mRNAs , as demonstrated in yeast . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Activation of GCN 2 results in increased phosphorylation of the alpha subunit of eIF 2 , which in turn causes inhibition of eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Up regulated expression of eIF 2 beta mRNA was confirmed by reverse Northern dot blot analysis . eIF 2 beta , together with eIF 2 alpha and eIF 2 gamma , comprise subunits of a complex that promotes the binding of methionyl tRNA to ribosomes during the initiation of protein translation . ^^^ The nucleotide sequence of the chick eIF 2 beta cDNA predicts a protein of 334 amino acids that has 95 % , 93 % , 56 % and 37 % sequence identity with rabbit , human , drosophila and yeast eIF 2 beta , respectively . ^^^ The deduced eIF 2 beta protein contains a number of functional motifs and domains consistent with the putative function of this protein ; these include a potential C 2 C2 zinc finger binding domain , three polylysine regions , and three acidic regions . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Catalysis of guanine nucleotide exchange on eIF 2 by eIF2B : can it be both a substituted enzyme and a sequential mechanism . ^^^ There are conflicting reports over the question of whether the displacement by GTP of GDP bound to eIF 2 catalyzed by eIF2B follows a substituted enzyme mechanism , as is believed to be the case for other guanine nucleotide exchange factors , or is a sequential mechanism . ^^^ Chem . 276 , 24697 24703 , 2001 ) showing displacement by eIF2B of GDP bound to eIF 2 in the absence of displacing nucleotide appears to offer a way of resolving the dispute and suggests that both mechanisms may be operative . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
An alternative mechanism for regulating eIF2B is through phosphorylation of the alpha subunit of eIF 2 , which converts it into an inhibitor of eIF2B . ^^^ CCK , CCh , A 23187 , and thapsigargin all enhanced eIF2alpha phosphorylation , suggesting that eIF2B activity is regulated by eIF2alpha phosphorylation under these conditions . ^^^ Removal of Ca ( 2+ ) from the medium enhanced the inhibitory action of CCK on both protein synthesis and eIF2B activity as well as further increasing eIF2alpha phosphorylation . ^^^ Although it is likely that other mechanisms account for the stimulation of acinar protein synthesis , these results suggest that the inhibition of acinar protein synthesis by CCK occurs as a result of depletion of Ca ( 2+ ) from the endoplasmic reticulum lumen leading to phosphorylation of eIF2alpha and inhibition of eIF2B . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The unsolved patients were investigated by mutation analysis of the genes encoding the alpha , gamma , and delta subunit of eIF2B and the gene encoding the alpha subunit of eIF 2 , because phosphorylation of this latter subunit regulates eIF2B activity . ^^^ Mutations were found in the genes encoding the alpha ( 1 patient ) , gamma ( 2 patients ) , and delta subunits ( 2 patients ) of eIF2B , but no mutations were found in the gene encoding the alpha subunit of eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Here , we reported that the first and the third SH 3 domains of Nck 1 interact with the C terminal region of the beta subunit of the eukaryotic initiation factor 2 ( eIF 2 beta ) . ^^^ Binding of eIF 2 beta was specific to the SH 3 domains of Nck 1 , and in vivo , the interaction Nck / eIF2 beta was demonstrated by reciprocal coimmunoprecipitations . ^^^ In addition , Nck was detected in a molecular complex with eIF 2 beta in an enriched ribosomal fraction , whereas no other SH2 / SH3 domain containing adapters were found . ^^^ This effect of Nck 1 required the integrity of its first and third SH 3 domains originally found to interact with eIF 2 beta . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Histidine limitation in the presence of histidinol induced a twofold increase in the phosphorylation of eIF2alpha and a concomitant reduction in eIF2B activity in perfused livers from wild type mice , but no changes in livers from Gcn 2 ( / ) mice . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
For protein synthesis initiation in eukaryotes , eIF2B is the guanine nucleotide exchange factor for eIF 2 . eIF2B is an essential multi subunit factor and a major target for translational control in both yeast and mammalian cells . ^^^ Finally , we show that the catalytic domain can provide eIF2B biological function in vivo when elevated levels eIF 2 and tRNA ( 1 ) ( Met ) are also present . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In the present study , we show in both NIH 3T3 cells and mouse embryo fibroblasts that stress granules contain not only eIF 2 but also the guanine nucleotide exchange factor for eIF 2 , eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The guanine nucleotide exchange activity of eIF2B was repressed , phosphorylation of the alpha subunit of eIF 2 was enhanced , and phosphorylation of eIF4E binding protein 1 and ribosomal protein S 6 kinase was reduced . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We found that the vast majority of translation initiation factors ( eIF 2 , eIF2B , eIF 3 , eIF4A1 , eIF 5 and eIF5B ) , all three elongation factors ( eEF1A , eEF1B and eEF 2 ) and the termination factor eRF 1 are strictly excluded from nuclei . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In this study , we investigated ischemia induced changes in protein levels and phosphorylation states of the initiation factors eIF2alpha , eIF2B epsilon , and eIF4G1 and of p 70 S6 kinase , proteins playing a central role in the control of the initiation of translation . ^^^ Transient ischemia caused a long lasting suppression of global protein synthesis . eIF2alpha was transiently phosphorylated after ischemia , peaking at 1 3 h of recovery . eIF2B epsilon and p 70 S6 kinase were completely dephosphorylated during ischemia and phosphorylation did not recover completely following reperfusion . ^^^ Thus , several different processes contributed to ischemia induced suppression of the initiation of protein synthesis : a long lasting dephosphorylation of eIF2B epsilon and p 70 S6K starting during ischemia , a transient phosphorylation of eIF2alpha during early reperfusion , and a marked decrease of eIF2B epsilon , eIF4G1 , and p 70 S6K protein levels starting during vascular occlusion ( eIF4G1 ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Regions corresponding to the human phosphorylation and kinase docking sites are identical in the proteins of both fish species , as are residues that interact with the eIF 2 recycling factor , eIF2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Caerulein inhibited the two major regulatory points of translation initiation : the activity of the guanine nucleotide exchange factor eIF2B ( with an increase of eIF2alpha phosphorylation ) and the formation of the eIF4F complex due , in part , to degradation of eIF4G . ^^^ Thus the inhibition of pancreatic protein synthesis in this model of AP most likely results from the inhibition of translation initiation as a result of increased eIF2alpha phosphorylation , reduction of eIF2B activity , and the inhibition of eIF4F complex formation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Events regulating the binding of initiator methionyl tRNA to the 40S ribosomal subunit were assessed through eIF2B activity and eIF 2 alpha phosphorylation on Ser 51 . ^^^ No differences were noted with either eIF2B or eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Burn failed to alter eIF2B activity or the total amount or phosphorylation status of either eIF 2 alpha or eIF2B epsilon in heart . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Structure of the archaeal translation initiation factor aIF 2 beta from Methanobacterium thermoautotrophicum : implications for translation initiation . aIF 2 beta is the archaeal homolog of eIF 2 beta , a member of the eIF 2 heterotrimeric complex , implicated in the delivery of Met tRNA ( 1 ) ( Met ) to the 40S ribosomal subunit . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Our findings imply CACH / VWM mutations do not specifically impair responses to eIF 2 phosphorylation , but instead cause protein structure defects that impair eIF2B activity . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
To examine the properties of archaeal initiation factor 2 alpha ( aIF 2 alpha ) , three genes encoding alpha , beta , and gamma subunits of aIF 2 from the hyperthermophilic archaeon Pyrococcus horikoshii OT 3 were expressed in Escherichia coli cells , and the resulting proteins , aIF 2 alpha , aIF 2 beta , and aIF 2 gamma , were characterized with reference to the properties of eIF 2 . aIF 2 alpha preferentially interacts with aIF 2 gamma , but does not interact with aIF 2 beta , which is consistent with data obtained with eIF 2 , of which eIF 2 gamma serves as a core subunit , interacting with eIF 2 alpha and eIF 2 beta . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic translation initiation factor 2B ( eIF2B ) is the guanine nucleotide exchange factor for eukaryotic initiation factor 2 ( eIF 2 ) . eIF2B is a heteropentameric protein composed of alpha subunits . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Surprisingly , during this period protein synthesis , relative RNA content , eIF2B activity , relative eIF 2 expression , and S6K1 phosphorylation all increased . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Translational control is exerted primarily during initiation by two mechanisms : 1 ) through inhibition of translation initiation complex formation via sequestration of the cap binding protein , eukaryotic initiation factor ( eIF ) 4E , with inhibitory 4E binding proteins ( 4E BP ) ; and 2 ) by prevention of eIF 2 GTP tRNA ( 1 ) ( Met ) formation and eIF2B activity by phosphorylated eIF2alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor eIF 2 and its ' exchange factor ' eIF2B play a key role in the regulation of protein synthesis in eukaryotes from yeast to mammals . ^^^ Phosphorylation of eIF 2 inhibits eIF2B and thus translation initiation . ^^^ The importance of correct control of eIF 2 and eIF2B for normal physiology is exemplified by data from transgenic mice carrying knock in or knock out mutations and by the fact that mutations in the genes for the eIF 2 kinase PERK or for eIF2B give rise to serious human diseases . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylated eIF 2 is an inhibitor of its guanine nucleotide exchange factor , eIF2B . ^^^ Thus , two structurally distinct effectors of eIF 2 function , eIF2alpha kinases and eIF2B , have evolved to recognize the same surface and overlapping determinants on eIF2alpha . . ^^^ PKR and GCN 2 kinases and guanine nucleotide exchange factor eukaryotic translation initiation factor 2B ( eIF2B ) recognize overlapping surfaces on eIF2alpha . ^^^ In contrast , mutations that blocked translational regulation but not Ser 51 phosphorylation impaired the binding of eIF2B to phosphorylated eIF2alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Both responses are elicited by phosphorylation of translation initiation factor 2 ( eIF 2 ) and the attendant inhibition of its nucleotide exchange factor eIF2B decreasing the binding to 40S ribosomes of methionyl initiator tRNA in the ternary complex ( TC ) with eIF 2 and GTP . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We show that although the cells expressing mutant eIF2B genes respond normally to stress conditions by reduced global translation rates , they exhibit significantly greater increase in ATF 4 induction compared to normal controls despite equal levels of stress and activity of the upstream eIF2alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Dynamic cycling of eIF 2 through a large eIF2B containing cytoplasmic body : implications for translation control . ^^^ The eukaryotic translation initiation factor 2B ( eIF2B ) provides a fundamental controlled point in the pathway of protein synthesis . eIF2B is the heteropentameric guanine nucleotide exchange factor that converts eIF 2 , from an inactive guanosine diphosphate bound complex to eIF 2 guanosine triphosphate . ^^^ Here we demonstrate that in contrast to other translation initiation factors , eIF2B and eIF 2 colocalize to a specific cytoplasmic locus . ^^^ Indeed eIF 2 shuttles into these foci whereas eIF2B remains largely resident . ^^^ Three different strategies to decrease the guanine nucleotide exchange function of eIF2B all inhibit eIF 2 shuttling into the foci . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The large spectrum of eIF2B related diseases . eIF2B ( eukaryotic initiation factor 2B ) is a GEF ( guanine nucleotide exchange factor ) that plays , with its substrate eIF 2 , a key regulatory role in the translation initiation phase of protein synthesis . ^^^ The importance of correct control of eIF 2 and eIF2B for normal physiology is underlined by the recent involvement of the five genes that encode the five eIF2B subunits in a severe autosomal recessive neurodegenerative disease , described in young children as CACH ( childhood ataxia with central nervous system hypomyelination ) / VWM ( leukoencephalopathy with vanishing white matter ) syndrome . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Interaction of recombinant human eIF 2 subunits with eIF2B and eIF2alpha kinases . ^^^ Consistent with this observation , the beta subunit specifically interacts with the purified eIF2B in ELISA studies and this interaction is enhanced when wt eIF2alpha in the recombinant trimeric complex is phosphorylated or replaced by a mutant phosphomimetic eIF2alpha ( S51D ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We examined whether supplementation of HeLa cell extracts with any translation initiation factor or translational regulator could enhance protein synthesis . eIF 2 ( eukaryotic translation initiation factor 2 ) and eIF2B augmented translation of capped , uncapped and encephalomyocarditis virus internal ribosome entry site promoted mRNAs . eIF4E specifically stimulated capped mRNA translation , while p 97 , a homologue to the C terminal two thirds of eIF4G , increased uncapped mRNA translation . ^^^ When the HeLa cell extract was supplemented with a combination of eIF 2 , eIF2B , and p 97 , the capacity to synthesize a protein from an uncapped mRNA became comparable to that from the capped counterpart stimulated with a combination of eIF 2 , eIF2B , and eIF4E . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This is accompanied by inhibition of activity of the guanine nucleotide exchange factor eIF2B that is responsible for GDP GTP exchange on eIF 2 . ^^^ At lower doses , neither eIF2alpha phosphorylation nor eIF2B activity is altered . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The factor eIF 5 stimulates hydrolysis of GTP by eIF 2 upon AUG codon recognition , whereas the factor eIF2B promotes guanine nucleotide exchange on eIF 2 to recycle the factor for additional rounds of translation initiation . ^^^ The GTP binding ( G ) domain resides in the gamma subunit of the heterotrimeric eIF 2 ; however , only eIF2beta , and not eIF2gamma , has been reported to directly bind to eIF 5 or eIF2B . ^^^ Thus , rather than allosterically regulating eIF2gamma G domain function via eIF2beta , our data support a model in which the GTPase activating factor eIF 5 and the guanine nucleotide exchange factor eIF2B modulate eIF 2 function through direct interactions with the eIF2gamma G domain . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Since eIF2B is required for recycling of eIF 2 , a factor required for all cytoplasmic translation initiation events , this will contribute to overall activation of protein synthesis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Recently , we have found that the eIF2B guanine nucleotide exchange factor resides in a specific cytoplasmic focus in the yeast , Saccharmoyces cerevisiae . eIF2B is a resident feature of this focus , whereas eIF 2 shuttles to and fro . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The IF 5 CTD interacts directly with the translation initiation factors eIF 1 , eIF 2 beta , and eIF3c , thus forming together with eIF 2 bound Met tRNA ( 1 ) ( Met ) the MFC . ^^^ The binding sites of eIF 2 beta , eIF 3 and eIF 1 were mapped onto the structure . eIF 2 beta and eIF 3 bind to non overlapping patches of negative and positive electrostatic potential , respectively . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
GDP binds the pentameric factor eIF2B for guanine nucleotide exchange . eIF 5 and the eIF2Bvarepsilon catalytic subunit possess a conserved eIF 2 binding site . ^^^ Nearly half of cellular eIF 2 forms a complex with eIF 5 lacking Met tRNA ( 1 ) ( Met ) , and here we investigate its physiological significance . eIF 5 overexpression increases the abundance of both eIF2 / eIF5 and TC / eIF5 complexes , thereby impeding eIF2B reaction and MFC formation , respectively . eIF2Bvarepsilon mutations , but not other eIF2B mutations , enhance the ability of overexpressed eIF 5 to compete for eIF 2 , indicating that interaction of eIF2Bvarepsilon with eIF 2 normally disrupts eIF2 / eIF5 interaction . ^^^ We propose that the eIF2 / eIF5 complex represents a cytoplasmic reservoir for eIF 2 that antagonizes eIF2B promoted guanine nucleotide exchange , enabling coordinated regulation of translation initiation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Truncated protein phosphatase GLC 7 restores translational activation of GCN 4 expression in yeast mutants defective for the eIF 2 alpha kinase GCN 2 . ^^^ The truncated form of GLC 7 does not suppress the regulatory defect associated with a gcn 2 deletion or a mutation in the phosphorylation site of eIF 2 alpha ( Ser 51 ) . ^^^ These findings suggest that the phosphatase activity of GLC 7 acts in opposition to the kinase activity of GCN 2 in modulating the level of eIF 2 alpha phosphorylation and the translational efficiency of GCN 4 mRNA . ^^^ This conclusion is supported by biochemical studies showing that the truncated GLC 7 allele increases the level of eIF 2 alpha phosphorylation in the gcn 2 507 mutant to a level approaching that seen in wild type cells under starvation conditions . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The role of eukaryotic initiation factor 2 ( eIF 2 ) phosphorylation in translational control has been demonstrated in vivo by overexpressing variant forms of eIF 2 alpha that are not phosphorylated . ^^^ COS 1 cells transiently transfected with expression vectors for human eIF 2 alpha contain 10 20 fold more eIF 2 alpha subunit than the endogenous COS cell eIF 2 trimeric complex . ^^^ Expression of the variant form of eIF 2 alpha , Ser51Asp , where Asp replaces Ser 51 , causes inhibition of protein synthesis , whereas the Ser48Asp variant does not . ^^^ When either Ser 48 or Ser 51 is replaced by Ala , the variants stimulate dihydrofolate reductase synthesis when the eIF 2 alpha kinase , DAI , is activated . ^^^ In order to elucidate these mechanisms , we have separated eIF 2 trimeric complexes from free overexpressed eIF 2 alpha subunits by fast protein liquid chromatography Superose chromatography . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The eukaryotic initiation factor 2 ( eIF 2 ) associated 67 kDa polypeptide ( p 67 ) isolated from reticulocyte lysate protects the eIF 2 alpha subunit from eIF 2 kinase catalyzed phosphorylation and promotes protein synthesis in the presence of active eIF 2 kinases . ^^^ The results are as follows . ( 1 ) Both p 67 and eIF 2 kinase ( s ) are present in active forms in all animal cells under normal growth conditions and p 67 protects the eIF 2 alpha subunit from eIF 2 kinase catalyzed phosphorylation , thus promoting protein synthesis in the presence of active eIF 2 kinases . ( 2 ) In heme deficient reticulocyte lysates and in serum starved KRC 7 cells in culture , p 67 is deglycosylated and subsequently degraded . ^^^ This leads to eIF 2 kinase catalyzed eIF 2 alpha subunit phosphorylation and thus to protein synthesis inhibition . ( 3 ) Addition of a mitogen ( namely , phorbol 12 myristate 13 acetate ) to serum starved KRC 7 cells in culture induces an increase of p 67 and thus increases protein synthesis . ^^^ The heme regulated inhibitor is present in an active form and possibly in equal amounts in both heme deficient and heme supplemented reticulocyte lysates but can not phosphorylate eIF 2 alpha subunit because of the presence of p 67 . ( 2 ) p 67 is essential for protein synthesis as it protects the eIF 2 alpha subunit from eIF 2 kinase catalyzed phosphorylation and promotes protein synthesis in the presence of one or more active eIF 2 kinases present in all animal cells . ( 3 ) p 67 is both degradable and inducible . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Interferon resistance of vaccinia virus is mediated by specific inhibition of phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) by the double stranded RNA activated ( DAI ) protein kinase . ^^^ Vaccinia virus encodes a homolog of eIF 2 alpha , K3L , the deletion of which renders the virus sensitive to interferon treatment . ^^^ We have studied the mechanism by which this protein product elicits interferon resistance in a transient DNA transfection system designed to evaluate regulators of eIF 2 alpha phosphorylation . ^^^ The K3L protein inhibits eIF 2 alpha phosphorylation and DAI kinase activation , apparently without being phosphorylated itself . ^^^ Inhibition of protein synthesis , elicited by expression of a mutant Ser 51 Asp eIF 2 alpha designed to mimic a phosphorylated serine , is not relieved by the presence of K3L , suggesting that K3L can not bypass a block imposed by eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have obtained highly purified preparations of the heme controlled eukaryotic initiation factor 2 alpha subunit ( eIF 2 alpha ) kinase ( HCI ) from rabbit reticulocyte lysates containing five different polypeptides . ^^^ In agreement with this , monoclonal antibodies directed against p 87 do not interfere with eIF 2 alpha kinase activity . ^^^ Upon incubation of the HCI preparation with hemin ( 5 10 microM ) , the eIF 2 alpha kinase is converted into an inactive form and appears to become associated with related peptides forming high molecular weight complexes which can be reversibly activated by 2 mercaptoethanol . ^^^ The data strongly suggest that hemin regulates eIF 2 alpha kinase activity by promoting formation of the inactive dimer HCI . p87 via disulfide bonds and direct binding of hemin . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Effects of hemin and porphyrin compounds on intersubunit disulfide formation of heme regulated eIF 2 alpha kinase and the regulation of protein synthesis in reticulocyte lysates . ^^^ To study the mechanism by which heme regulates the heme regulated eIF 2 alpha kinase ( HRI ) , the effects of various protoporphyrin 9 ( PP ) compounds on the kinase activities and intersubunit disulfide formation of HRI and on protein synthesis in reticulocyte lysates were examined . ^^^ Hemin and cobalt protoporphyrin ( CoPP ) are more effective than ZnPP , NiPP , SnPP , and metal free PP in promoting intersubunit disulfide bond formation in HRI , in inhibiting the autokinase and eIF 2 alpha kinase activities of HRI , in inhibiting phosphorylation of eIF 2 alpha in rabbit reticulocytes , in maintaining protein synthesis , and in reversing the inhibition of protein synthesis in heme deficiency . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the alpha subunit ( 38 kDa ) of eukaryotic initiation factor 2 ( eIF 2 alpha ) regulates initiation of protein synthesis in eukaryotic cells . ^^^ Further , isolated polysomes contain eIF 2 alpha that is efficiently phosphorylated in vitro by heme regulated inhibitor ( HRI ) . ^^^ These findings suggest that polysome bound eIF 2 alpha is a target of HRI under physiological conditions . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
During mitogenic activation , the level of eIF 2 alpha mRNA increases at least 50 fold , an effect thought to be due primarily to intranuclear stabilization of the primary transcript ( Cohen , R . ^^^ This Inr element is positioned 450 bases downstream of the eIF 2 alpha promoter and is oriented to generate an overlapping antisense transcript . ^^^ Deletion or mutation of the Inr element results in a reproducible 5 8 fold increase in the activity of an eIF 2 alpha promoter driven CAT reporter gene and a corresponding 2 . 5 fold decrease in activity of an antisense driven luciferase reporter gene in vivo in 293 cells . ^^^ A potential role for double stranded RNA generated by these overlapping divergent transcription units in the regulation of eIF 2 alpha gene expression in T cells is suggested . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The 58 kDa inhibitor did not function by degrading or sequestering the dsRNA activator of P 68 but could repress phosphorylation of eIF 2 alpha by an already activated protein kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Finally , slot blot analysis of polyadenylated RNA revealed no significant change in the relative abundance of eIF 2 alpha mRNA with age . ^^^ The last mentioned experiments suggest that the synthesis of eIF 2 may be regulated through changes in the deficiency of translation of eIF 2 alpha mRNA rather than through changes in gene transcription . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Translational initiation factors IF 1 and eIF 2 alpha share an RNA binding motif with prokaryotic ribosomal protein S 1 and polynucleotide phosphorylase . ^^^ Using the technique of profile analysis , the S 1 RM can also be found in bacterial and chloroplast translation initiation factor IF 1 sequences , and in the sequences of eukaryotic translation initiation factor eIF 2 alpha chains . ^^^ The most obvious common function of the proteins containing the S 1 RM seems to be RNA binding , suggesting that IF 1 and eIF 2 alpha may bind to RNA . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Although considerable evidence demonstrates that translational initiation can be regulated at the post translational level by the phosphorylation / dephosphorylation of translation initiation factors ( eIFs ) such as eIF 4E and eIF 2 alpha , additional mechanisms of eIF gene expression may also play a role in the regulation of translation in quiescent cells and / or during their subsequent induction to enter the cell cycle . ^^^ To address this issue , gene expression of eIF 2 alpha , 4E , and 4A was studied in quiescent human peripheral blood T cells following stimulation through the T cell receptor CD 3 complex . ^^^ Quiescent T cells expressed low levels of eIF 2 alpha , 4E , and 4A mRNAs and proteins as compared to proliferating T cells . ^^^ Western blot analysis also showed that the protein levels of the three eIFs were differentially increased . eIF 4A protein levels increased in proportion to the observed increase in cellular protein synthetic activity while the increases in eIF 4E and eIF 2 alpha proteins were proportionately less . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
COS cells transfected with plasmids that activate DAI depend on expression of virus associated 1 ( VAI ) RNA to prevent the inhibitory effects of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) kinase ( DAI ) and restore the translation of vector derived dihydrofolate reductase mRNA . ^^^ In dl 331 infected 293 cells , eIF 2 alpha was present mainly in the acidic , phosphorylated form , and trans complementation with polypeptide sigma 3 or VAI RNA decreased the proportion of eIF 2 alpha ( P ) from approximately 85 to approximately 30 % . ^^^ Although the proportion of eIF 2 alpha ( P ) was greater than that in uninfected cells , most of the factor remained in the unphosphorylated form , even at 16 h after infection , consistent with the partial inhibition of host protein synthesis observed with all three viral serotypes . ^^^ The results indicate that reovirus polypeptide sigma 3 participates in the regulation of protein synthesis by modulating DAI and eIF 2 alpha phosphorylation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Mutations activating the yeast eIF 2 alpha kinase GCN 2 : isolation of alleles altering the domain related to histidyl tRNA synthetases . ^^^ The protein kinase GCN 2 stimulates expression of the yeast transcriptional activator GCN 4 at the translational level by phosphorylating the alpha subunit of translation initiation factor 2 ( eIF 2 alpha ) in amino acid starved cells . ^^^ Phosphorylation of eIF 2 alpha reduces its activity , allowing ribosomes to bypass short open reading frames present in the GCN 4 mRNA leader and initiate translation at the GCN 4 start codon . ^^^ Representative mutations in each domain were shown to depend on the phosphorylation site in eIF 2 alpha for their effects on GCN 4 expression and to increase the level of eIF 2 alpha phosphorylation in the absence of amino acid starvation . ^^^ The phenotypes of the GCN2c alleles are dependent on GCN 1 and GCN 3 , indicating that these two positive regulators of GCN 4 expression mediate the inhibitory effects on translation initiation associated with activation of the yeast eIF 2 alpha kinase GCN2 . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The RNA dependent P1 / eIF 2 alpha protein kinase is a highly specific protein serine / threonine kinase that catalyzes the phosphorylation of the alpha subunit of protein synthesis initiation factor eIF 2 . ^^^ Certain RNAs are able to activate the eIF 2 alpha kinase activity inherent within protein P 1 , a process which involves an autophosphorylation of protein P 1 , whereas other RNAs are able to antagonize the activation process . ^^^ Translational repression mediated by the kinase may also be disrupted by RNA binding proteins that sequester activator double stranded RNAs and by site directed mutants and homologs of the eIF 2 alpha translation factor substrate . ^^^ The P1 / eIF 2 alpha protein kinase is an important regulator of the translation of plasmid derived mRNAs in transfected eukaryotic cells . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
With continued exposure to A 23187 ( 3 h ) rates of amino acid incorporation partially recovered , eIF 2 alpha became dephosphorylated , and the inhibition of eIF 2B activity was abolished . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This inhibition has been demonstrated to be due primarily to the activation of the heme regulated eIF 2 alpha kinase ( HRI ) which causes an arrest in the initiation of translation . ^^^ A comparison of two lysate preparations , which had a 2 fold difference in their protein synthesis rates , indicated that the slower translational rate of the one lysate could be accounted for by its low level of constitutive eIF 2 alpha phosphorylation , with its accompanying decrease in the eIF 2B activity and lower level of polyribosome loading . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The best characterized mechanism for regulating GEF activity is through changes in the phosphorylation of the smallest subunit of eIF 2 ( eIF 2 alpha ) ; however , none of the stimuli studied altered the level of phosphorylation of eIF 2 alpha in Swiss fibroblasts . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Microcystin was also found to increase the phosphorylation of eIF 2 alpha ( and therefore to inhibit initiation ) at lower concentrations than okadaic acid , suggesting that the major eIF 2 alpha phosphatase in the reticulocyte lysate is phosphatase 1 . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The increase in the amount of eIF 2 alpha in the phosphorylated form apparently was not due to an increase in kinase activity , because there was no change in eIF 2 alpha kinase activity in extracts of liver perfused with medium containing histidinol compared to controls . ^^^ Instead , the increased phosphorylation of eIF 2 alpha was associated with an inhibition of eIF 2 alpha phosphatase activity . ^^^ Thus , in contrast to other systems that have been examined , the mechanism involved in the increase in the phosphorylation state of eIF 2 alpha appears to involve an inhibition of eIF 2 alpha phosphatase activity rather than activation of an eIF 2 alpha kinase . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have purified the heme regulated eukaryotic initiation factor 2 alpha subunit ( eIF 2 alpha ) kinase ( HRI ) from rabbit reticulocytes for amino acid microsequencing . ^^^ Its functions of binding ATP and of autophosphorylation and eIF 2 alpha phosphorylation are inhibited by hemin . ^^^ These findings are consistent with the autokinase and eIF 2 alpha kinase activities of HRI . ^^^ Synthetic HRI peptide P 74 is a very potent inhibitor of eIF 2 alpha phosphorylation by HRI . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The alpha subunit of eukaryotic protein synthesis initiation factor ( eIF 2 alpha ) is phosphorylated at a single serine residue ( Ser 51 ) by two distinct and well characterized protein kinase , the haem controlled repressor ( HCR ) and the double stranded RNA activated inhibitor ( dsI ) . ^^^ These findings are consistent with the disposition of basic residues near the phosphorylation site in eIF 2 alpha and show that the specificities of HCR and dsI differ from other protein kinases whose specificities have been studied . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Tissue distribution and immunoreactivity of heme regulated eIF 2 alpha kinase determined by monoclonal antibodies . ^^^ A highly purified preparation of heme regulated inhibitor ( HRI ) , an eIF 2 alpha kinase , from rabbit reticulocyte lysates has been used for generating monoclonal antibodies ( mAB ) . ^^^ In in vitro protein kinase assays , preincubation of HRI with the antibodies significantly diminished both autokinase and eIF 2 alpha kinase activities . ^^^ The antibodies did not detect cross reacting HRI in rat or human reticulocytes or in mouse erythroleukemic cells or human K 562 cells even after induction of differentiation , although eIF 2 alpha kinase activity was detected in them . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Partial characterization of a cellular factor that regulates the double stranded RNA dependent eIF 2 alpha kinase in 3T3 F442A fibroblasts . ^^^ The interferon induced double stranded RNA dependent eIF 2 alpha kinase ( dsI ) has an established role in mediating part of interferon ' s antiviral effects . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A peptide P ( 45 56 ) corresponding to residues 45 56 ( sequence : ILLSELSRRRIR ) of eIF 2 alpha was synthesised . ^^^ It was phosphorylated by both of the well characterised eIF 2 alpha kinases viz . ; the heme controlled repressor ( HCR ) and the double stranded RNA dependent inhibitor ( dsI ) . ^^^ Only the residue corresponding to serine 51 in eIF 2 alpha was phosphorylated by HCR , dsI or PKC . ^^^ The phosphorylation of the peptide by dsI and the phosphorylation of eIF 2 alpha by dsI or HCR showed sigmoidal kinetics with respect to substrate concentration . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Cloning of the cDNA of the heme regulated eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) kinase of rabbit reticulocytes : homology to yeast GCN 2 protein kinase and human double stranded RNA dependent eIF 2 alpha kinase . ^^^ We have cloned the cDNA of the heme regulated eIF 2 alpha kinase ( HRI ) of rabbit reticulocytes . ^^^ In vitro translation of mRNA transcribed from the HRI cDNA yields a 90 kDa polypeptide that exhibits eIF 2 alpha kinase activity and is recognized by a monoclonal antibody directed against authentic HRI . ^^^ The HRI cDNA coding sequence has extensive homology to GCN 2 protein kinase of Saccharomyces cerevisiae and to human double stranded RNA dependent eIF 2 alpha kinase . ^^^ This observation suggests that GCN 2 protein kinase may be an eIF 2 alpha kinase in yeast . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The data presented here show that serine 51 of the alpha subunit of eukaryotic initiation factor eIF 2 is the only residue phosphorylated by the eIF 2 alpha specific kinases HCR ( haem controlled repressor ) and dsI ( double stranded RNA activated inhibitor ) in vitro . ^^^ Methodology appropriate for the examination of phosphorylation sites in eIF 2 alpha in whole cells and their extracts has been developed , and used to study the site ( s ) in eIF 2 alpha labelled in reticulocyte lysates . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We show that viral suppression of cellular protein synthesis occurs concomitant with activation of the interferon induced double stranded RNA activated inhibitor ( DAI ) , a protein kinase , and phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) , but that prevention of host cell shut off by 2 aminopurine occurs without a decrease in kinase activity or a dephosphorylation of eIF 2 alpha . ^^^ Results are presented that indicate that activation of DAI kinase and phosphorylation of eIF 2 alpha may be required but are not sufficient to achieve inhibition of cellular protein synthesis during adenovirus infection . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Increased eIF 2 alpha expression in mitogen activated primary T lymphocytes . ^^^ G 0 human T cells synthesize protein at low rates and contain very low levels of eIF 2 alpha mRNA . eIF 2 alpha plays a pivotal role in the earliest regulated steps of translation initiation . ^^^ We examined eIF 2 alpha gene expression in normal human T cells stimulated with PHA . ^^^ Nuclear run on assays indicate low rates of eIF 2 alpha gene transcription in G 0 cells and these change 2 fold with PHA treatment . ^^^ Actinomycin D chase experiments show that the t1 / 2 of eIF 2 alpha mRNA is similar in G 0 and PHA treated T cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Activation of the double stranded RNA dependent eIF 2 alpha kinase by cellular RNA from 3T3 F442A cells . ^^^ The interferon induced double stranded RNA dependent eIF 2 alpha kinase has an established role in mediating part of interferons anti viral effects . ^^^ We demonstrate here that total cytoplasmic RNA from 3T3 F442A cells contains a regulatory RNA ( s ) capable of activating dsRNA dependent eIF 2 alpha kinase . ^^^ It bound tightly to the dsRNA dependent eIF 2 alpha kinase and was immune precipitated with its antibodies as a complex of regulatory RNA and dsRNA dependent eIF 2 alpha kinase . ^^^ These findings indicated that the regulatory RNA forms a specific complex with the dsRNA dependent eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In vivo , phosphorylation of eIF 2 alpha increases in response to amino acid starvation , which is dependent on GCN 2 . ^^^ Substitution of Ser 51 with alanine eliminates phosphorylation of eIF 2 alpha by GCN 2 in vivo and in vitro and abolishes increased expression of GCN 4 and amino acid biosynthetic genes under its control in amino acid starved cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A human eIF 2 alpha cDNA ( encoding alpha subunit of the eukaryotic initiation factor 2 ) was expressed under the control of the galactose regulated GAL 1 , 10 promoter , in Saccharomyces cerevisiae , in order to study the possible interactions of human eIF 2 alpha with the yeast protein synthesis apparatus . ^^^ Isoelectric focusing coupled with Western blot analysis demonstrated that the human eIF 2 alpha subunit synthesized in yeast under a variety of growth conditions was detected as two bands which co migrated with the phosphorylated and unphosphorylated forms of rabbit eIF 2 alpha , suggesting covalent modification in vivo . ^^^ Cell fractionation studies further demonstrated that the synthesised human eIF 2 alpha protein , though present in the cytoplasm , was largely associated with the yeast ribosomes , but could be removed from these by washing with 0 . 3 M KCl . ^^^ Immunoreactive eIF 2 alpha was found in fractions with eIF 2 activity and the estimated molecular mass ( 130 kDa ) corresponded to that predicted for the eIF 2 trimer . ^^^ These analyses suggest that human eIF 2 alpha subunit synthesised in yeast can become involved with the yeast protein synthetic apparatus , though whether this is a functional incorporation requires further genetic studies . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
However , we have found no change in the phosphorylation state of eIF 2 alpha in either fast or slow twitch muscles from diabetic compared to control animals . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
However , as total eIF 2 accumulates , the ratio of phosphorylated eIF 2 alpha ( eIF 2 ( alpha P ] to eIF 2 alpha decreases . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have examined the phosphorylation of the alpha subunit of initiation factor 2 ( eIF 2 alpha ) in reticulocyte lysates in which translational shut off was induced by haem deficiency or by double stranded RNA . ^^^ To maximise the phosphorylation of eIF 2 alpha , lysates were supplemented with the broad spectrum phosphatase inhibitor microcystin . ^^^ This is consistent with the observation of only two species of eIF 2 alpha in isoelectric focusing / immunoblotting analyses of lysates treated as described above . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Two cDNA clones have been isolated , from a bovine lymphosarcoma library , that encode the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) . ^^^ The predicted 315 amino acid sequence showed more than 99 % amino acid identity with rat and human eIF 2 alpha . ^^^ Galactose regulated expression of a full length bovine eIF 2 alpha cDNA in yeast resulted in the synthesis of a polypeptide of the predicted molecular mass ( 36 kDa ) . ^^^ Furthermore , the expressed polypeptide cross reacted with an antibody raised against rabbit eIF 2 alpha confirming the identity of the cDNA . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The phosphorylation of purified regulin and eIF 2 by casein kinase 2 ( CK 2 ) and the heme sensitive eIF 2 alpha kinase , respectively , was also inhibited by the polyphenolic compound . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The gcd 2 503 mutation also results in polysome runoff , accumulation of inactive 80S ribosomal couples , and accumulation of at least one of the subunits of the general translation initiation factor 2 ( eIF 2 alpha ) in 43S 48S particles following a shift to the restrictive temperature . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Incubation of a temperature sensitive gcdl 101 mutant at the restrictive temperature led to a rapid reduction in the average size and quantity of polysomes , plus an accumulation of inactive 80S ribosomal couples ; in addition , excess amounts of eIF 2 alpha , GCD 1 , GCD 2 , and GCN 3 were found comigrating with free 40S ribosomal subunits . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Under conditions of inhibition of protein synthesis in situ by chloroquine in the culture , the parasite eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) is phosphorylated in the parasite lysate to a greater extent than that observed in the control culture . ^^^ Addition of hemin in vitro suppresses this phosphorylation . eIF 2 alpha kinase activity is present in the parasite lysate and is not a contaminant derived from the human erythrocytes used to culture the parasite . ^^^ The heme chloroquine interactive effects can also be demonstrated with purified eIF 2 alpha kinase from rabbit reticulocyte lysate . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The results suggest that protein synthesis in rat liver is regulated directly by changes in intracellular calcium concentration through a mechanism involving modulation of the phosphorylation state of eIF 2 alpha . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
These results suggest that high concentrations of EBER 1 regulate protein synthesis by blocking the activation of the double stranded RNA dependent eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) protein kinase DAI ( p 68 ) , and that this property is dependent on the secondary structure of the small RNA molecule . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Furthermore , in hepatocytes there was substantial type 2C phosphatase activity against EF 2 , but not against phosphorylase or eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
At higher concentrations ( 20 80 microM ) this inhibitor induces activation of an eukaryotic polypeptide chain initiation factor 2 alpha subunit ( eIF 2 alpha ) kinase in hemin supplemented reticulocyte lysates , as does hemin deficiency . ^^^ The presence of the disulfide bridges in gamma hordothionin appears to be essential for the eIF 2 alpha kinase activation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The results demonstrate the novel finding that the inhibition of protein synthesis in vasopressin treated livers is caused by a reduction in eIF 2B activity due to an increase in phosphorylation of eIF 2 alpha . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Inhibition of the initiation of hepatic protein synthesis during ethionine mediated ATP depletion in vivo : modification to ribosomal subunits , evidence of impaired ternary complex formation and a subcellular redistribution of eIF 2 alpha . ^^^ The application of quantitative western blotting demonstrates that the level of antigenic eIF 2 alpha in the microsomal salt wash extract increases 31 % during the inhibition . ^^^ These observations are consistent with the idea that the inhibition of the initiation of hepatic protein synthesis induced by ethionine is mediated by eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The 90 kDa component of reticulocyte heme regulated eIF 2 alpha ( initiation factor 2 alpha subunit ) kinase is derived from the beta subunit of spectrin . ^^^ Antibodies from three different lines of monoclonal hybridomas crossreact with both the beta subunit of spectrin and the 90 kDa peptide present in highly purified preparations of the heme controlled eIF 2 alpha ( initiation factor 2 alpha subunit ) kinase from rabbit reticulocytes . ^^^ We conclude that the 90 kDa peptide is derived by proteolysis from the beta subunit of spectrin , probably from its carboxyl terminus , and suggest that the heme sensitive eIF 2 alpha kinase , like the 56 kDa phosphatase [ Wollny , E . , Watkins , K . , Kramer , G . & Hardesty , B . ( 1984 ) J . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Haemin ( 40 microM ) as well as purified eukaryotic initiation factor 2 ( eIF 2 ) from rabbit reticulocytes enhance amino acid incorporation in both kinds of extracts , which suggests that both uninduced and induced MEL cells contain a haemin controlled eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have previously reported that cultured mouse 3T3 F442A cells exhibit a transient , double stranded RNA ( dsRNA ) dependent phosphorylation of the dsRNA dependent eIF 2 alpha kinase ( eIF 2 alpha , alpha subunit of the eukaryotic initiation factor 2 ) ( dsI ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
To explain this global inhibition of protein synthesis , the phosphorylation state of the alpha subunit of eucaryotic initiation factor 2 ( eIF 2 alpha ) was examined . eIF 2 alpha was phosphorylated in both R 2 2A 2 and wild type virus infected cells , indicating that poliovirus does not encode a function that blocks phosphorylation of eIF 2 alpha . ^^^ The kinetics and extent of eIF 2 alpha phosphorylation correlated with the production of double stranded RNA in infected cells , suggesting that eIF 2 alpha is phosphorylated by P1 / eIF 2 alpha kinase . ^^^ Since phosphorylation of eIF 2 alpha was not inhibited by 2 aminopurine , we propose that 2 aminopurine rescues the ability of R 2 2A 2 to induce cleavage of p 220 by inhibition of a second as yet unidentified kinase . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Enhanced phosphorylation of eIF 2 alpha was obvious at 9 h and increased by 12 h postinfection . ppp ( A2 ' p ) nA and ppp ( A2 ' p ) nA mediated rRNA cleavage were observed from 6 h . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The translational inhibition produced by addition of HS to hemin containing reticulocyte lysates and the accompanying phosphorylation of the eIF 2 alpha subunit can be prevented or reversed by NADPH generators including glucose 6 phosphate , NADPH itself , and also by dithiols , e . g . , dithiothreitol , but not by fructose 1 , 6 bisphosphate or by monothiols , e . g . , 2 mercaptoethanol . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have recently cloned and characterized the promoter region of the gene encoding eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) to identify regulatory elements of this housekeeping gene . ^^^ The eIF 2 alpha promoter contains four upstream DNase 1 HS sites extending from 650 to 40 base pairs and a fifth downstream site near the first intron exon junction . ^^^ To initiate our analysis of factors required for eIF 2 alpha expression , selected a CAP proximal element shown by in vivo methylation protection analysis to bind a potential regulatory factor . ^^^ When linked to a CAT reporter gene , activity of the eIF 2 alpha promoter shows an approximate 2 fold dependence on the alpha PAL element . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Activation of this kinase results in phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 alpha ) and correlates with inhibition of translation initiation . ^^^ In this report we show growth complementation of adenoviruses harboring deletions in the VAI gene in cell lines expressing a serine to alanine mutant of eIF 2 alpha . ^^^ These results directly show that the primary function of VAI RNA in the lytic adenovirus infection is the inhibition of eIF 2 alpha phosphorylation by DAI kinase and identify eIF 2 alpha as the target that mediates the effects of DAI kinase activation . ^^^ Cells that express a mutant eIF 2 alpha will enable the isolation of specific host range mutants for other types of viruses that are defective in the ability to inhibit DAI kinase . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) inhibits protein synthesis by competitively inhibiting the guanine nucleotide exchange factor ( GEF ) , and modulation of the extent of phosphorylation of eIF 2 alpha has been suggested as a probable regulatory mechanism in serum deprived mammalian cells . ^^^ We measured the ratio of phosphorylated to total eIF 2 alpha in serum deprived cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We also show that deletion of GCN 3 in sui 2 1 strains is lethal , suggesting that GCN 3 contributes to eIF 2 alpha function in addition to its role as a translational activator of GCN4 . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
First described in rabbit reticulocytes as inhibitors of translation , two distinct eIF 2 alpha kinases are known : the haemin controlled kinase ( termed HCI ) and the double stranded RNA activated kinase ( termed DAI ) . eIF 2 alpha phosphorylation appears to be a reversible control mechanism since corresponding phosphatases have been described . ^^^ Recent reports indicate a correlation between eIF 2 alpha phosphorylation and the inhibition of protein synthesis in several mammalian cell types under a range of physiological conditions . ^^^ In this review , the physical and functional features of the known eIF 2 alpha kinases are described with respect to their role in mammalian cells and the mode of activation by cellular signals . ^^^ Furthermore , the possible impact of the eIF 2 / eIF 2B ratio and of the subcellular compartmentation of these factors ( and the eIF 2 alpha kinases ) on mammalian protein synthesis is discussed . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The relative protein synthesis rates of eIF 4A and eIF 2 alpha were inhibited by about 70 % by the hormone , a reduction comparable to that for ribosomal proteins . ^^^ The mRNA levels of eIF 4A , eIF 4D , and eIF 2 alpha also were reduced by 60 to 70 % , indicating that synthesis rates are proportional to mRNA concentrations . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The inhibitor has no eIF 2 alpha phosphorylating activity and does not affect the formation of the ternary complex [ eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Similarly , under conditions of severe heat stress eIF 2 alpha and eIF 4B frequently recover to their prestress phosphorylation state before the recovery of protein synthesis . eIF 4E dephosphorylation likewise does not occur under mild heat stress conditions . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Presence of haemin controlled eIF 2 alpha kinases in both undifferentiated and differentiating mouse erythroleukaemia cells . ^^^ With purified eIF 2 as substrate , haemin controlled eIF 2 alpha kinases could be partially purified from cultured mouse erythroleukaemia cells ( MEL cells ) , which can be induced in vivo to erythroid differentiation . ^^^ The eIF 2 alpha kinases from both uninduced and induced MEL cells are clearly distinct from the double stranded RNA activated eIF 2 alpha kinase described for many mammalian cell types . ^^^ A rough quantitative estimation indicates that , on a per cell basis , induced MEL cells contain the same amount of haemin controlled eIF 2 alpha kinase activity as rabbit reticulocytes , whereas uninduced MEL cells contain about one tenth as much . ^^^ As to their chromatographic behavior on CM Sephadex and DEAE cellulose and their sensitivity towards physiological concentrations of haemin ( 5 10 microM ) , the eIF 2 alpha kinases from MEL cells are indistinguishable from HCI . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The promoter region of the gene ( eIF 2 alpha ) for eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) was isolated from a human genomic library and its structure was determined by restriction mapping and nucleotide ( nt ) sequence analysis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Nevertheless , reticulocyte lysates contain a potent PKC activity and we deemed it desirable to isolate this enzyme to answer unequivocally the question whether it does or does not activate eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Glucose 6 phosphate is required to maintain the activity of eukaryotic initiation factor ( eIF ) 2B by a mechanism that is independent of the phosphorylation of eIF 2 alpha . ^^^ Although there is a low level of phosphorylation of eIF 2 alpha in gel filtered lysate given hemin but no glucose 6 phosphate , it can not account for the loss of eIF 2B activity , since this phosphorylation is removed by antibody to the hemin controlled translational repressor or isocitrate , which do not restore protein synthesis or eIF 2B activity , and not by fructose 1 , 6 diphosphate , which does partially restore protein synthesis and eIF 2B activity . ^^^ Additional support for this conclusion is our finding that protein synthesis and eIF 2B activity in partially hemin deficient lysate can be restored by high levels of glucose 6 phosphate or fructose 1 , 6 diphosphate without a reduction in the level of phosphorylated eIF 2 alpha , suggesting that such levels of sugar phosphate may permit restoration of normal function with a limiting amount of eIF 2B . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A clone encoding the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) was isolated from a lambda gt 11 expression library of rat brain cDNAs . ^^^ The fusion protein expressed by the recombinant phage reacts with eIF 2 alpha antiserum except when the serum is preadsorbed with pure eIF 2 . ^^^ The translation of hybrid selected HeLa cell mRNA produces two proteins which are indistinguishable from authentic HeLa eIF 2 alpha and its phosphorylated form when analyzed by electrophoresis in two dimensional isoelectrofocusing / sodium dodecyl sulfate polyacrylamide gels and by partial protease digestion . ^^^ HeLa cell eIF 2 alpha mRNA migrates as a single band of about 1600 nucleotides . ^^^ The rat cDNA insert was sequenced , and the region coding for eIF 2 alpha was identified . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
When the eIF 2 alpha kinase is inhibited by 2 aminopurine , the mRNA is slowly transferred from 48 to 80 S initiation complexes after an initial lag . ^^^ This finding is discussed in view of the possible role of eIF 2 alpha kinase and endonuclease in the inhibition of viral mRNA translation in interferon treated cells . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The inhibition of globin synthesis in hemin deficient rabbit reticulocyte lysates is due to the activation of a hemin controlled translational inhibitor ( HCI ) that specifically phosphorylates eIF 2 alpha . ^^^ As for the preventive effect , it was observed that a ) the activation of HCI in the postribosomal supernatant of reticulocytes was prevented by GTP , but not by cAMP , and b ) cAMP and GTP inhibited the phosphorylation of eIF 2 alpha in hemin deficient lysates . ^^^ That is , cAMP inhibited the phosphorylation of eIF 2 alpha and promoted both the release of GDP from eIF 2 and the formation of eIF 2 ( alpha P ) 10 eIF 2B complex , and GTP prevented both the activation of HCI and the phosphorylation of eIF 2 alpha . ^^^ Though cAMP and GTP affected multiple steps , it is suggested that cAMP stimulates the globin synthesis by inhibiting the phosphorylation of eIF 2 alpha and that GTP stimulates the globin synthesis chiefly by preventing the activation of HCI in hemin deficient lysates . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A kinase able to phosphorylate exogenous protein synthesis initiation factor eIF 2 alpha is present in lysates of mengovirus infected L cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The inhibitions of protein synthesis initiation in heme deficient reticulocyte lysates and in GSSG treated hemin supplemented lysates are both characterized by the activation of heme regulated eIF 2 alpha kinase , which phosphorylates the alpha subunit of eukaryotic initiation factor ( eIF 2 ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The activity was , however , restored by combining both the three subunit eIF 2 and the 67 kDa polypeptide . ( 2 ) Active RF preparations contained eIF 2 alpha ( unphosphorylated ) and beta subunits and the 67 kDa polypeptide . ^^^ The 67 kDa polypeptide apparently protected eIF 2 alpha subunit from HRI catalyzed phosphorylation but did not inhibit HRI activity . ^^^ Based on these results , we suggest that the protein synthesis inhibition reversal activity in both eIF 2 and RF is due to the same components namely , eIF 2 alpha subunit and the 67 kDa polypeptide . ^^^ The 67 kDa polypeptide protects eIF 2 alpha subunit from HRI catalyzed phosphorylation and may also be a necessary component of the functioning eIF 2 molecule . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The inhibition of peptide chain initiation and 40S initiation complex formation in reticulocyte lysates under other conditions is associated with increased phosphorylation of the alpha subunit of protein synthesis initiation factor 2 ( eIF 2 alpha ) and the inhibition of recycling of this factor . ^^^ The addition of ethanol to reticulocyte lysates led to increased phosphorylation of eIF 2 alpha and to a decrease in the rate of exchange of guanine nucleotides bound to eIF 2 . ^^^ Taken together , these results suggest that ethanol leads to inhibition of peptide chain initiation both through increased phosphorylation of eIF 2 alpha and by directly inhibiting the productive interaction of eIF 2 and GEF . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Previously , we have shown that phosphorylation of the eukaryotic initiation factor eIF 2 alpha increases under several physiological stresses in which protein synthesis is inhibited in Ehrlich ascites tumor cells . ^^^ GEF activity was reduced from control values in extracts of heat shocked cells and serum deprived cells , concomitant with increased eIF 2 alpha phosphorylation . ^^^ GDP , the complete reversal of inhibition of GEF activity in heat shocked and serum deprived cells indicates that inhibition is due solely to phosphorylation of eIF 2 alpha . ^^^ In glutamine deprived cells phosphorylation of eIF 2 alpha was increased modestly and GEF activity was reduced but GEF activity could not be fully reversed by addition of eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Combined repression of P 68 function and eIF 2 alpha phosphorylation during influenza virus infection is essential for continued catalytic recycling of eIF 2 and efficient mRNA translation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The 90 kilodalton peptide of the heme regulated eIF 2 alpha kinase has sequence similarity with the 90 kilodalton heat shock protein . ^^^ Highly purified preparations of the heme controlled eIF 2 alpha ( eukaryotic peptide initiation factor 2 alpha subunit ) kinase of rabbit reticulocytes contain an abundant 90 kilodalton ( kDa ) peptide that is immunologically cross reactive with spectrin and that modulates the activity of the enzyme [ Kudlicki , W . , Fullilove , S . , Read , R . , Kramer , G . , & Hardesty , B . ( 1987 ) J . ^^^ The amino acid sequence of a tryptic phosphopeptide isolated by high performance liquid chromatography from the eIF 2 alpha kinase associated 90 kDa protein after phosphorylation by casein kinase 2 is shown to be identical with a 14 amino acid segment of the known sequence of the Drosophila 83 kDa heat shock protein . ^^^ Additional structural similarities between the eukaryotic heat shock proteins , the reticulocyte eIF 2 alpha kinase associated 90 kDa peptide , and spectrin are discussed . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The first step in the rescue of protein synthesis in inhibited lysates by hemin or MgGTP is the inhibition of heme regulated eIF 2 alpha kinase , which enables endogenous phosphatase to dephosphorylate eIF 2 ( alpha P ) and [ RF . eIF 2 ( alpha P ) ] . ^^^ Hemin and MgGTP both reverse inhibition by blocking the activation and / or activity of heme regulated eIF 2 alpha kinase in the lysate . ^^^ The conclusion that MgGTP exerts its effect on eIF 2 alpha kinase is supported by several in vitro findings : ( 1 ) 2 mM MgGTP inhibits the autophosphorylation of purified heme regulated eIF 2 alpha kinase and abolishes its ability to phosphorylate eIF 2 alpha ; ( 2 ) 2 mM MgGTP can not displace GDP in the binary complexes [ eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In this report we use a monoclonal antibody to identify the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) as a heat shock protein . ^^^ These results suggest that the induction of eIF 2 alpha in the heat shock response may be important for restoring the cell ' s ability to initiate protein synthesis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The phosphorylation state of the alpha subunit of initiation factor 2 ( eIF 2 alpha ) in Saccharomyces cerevisiae has been determined by two dimensional gel electrophoresis and autoradiography of lysates from cultures grown under a variety of conditions . ^^^ Only when cells were starved for a carbon source for 2 h in 1 M sorbitol was eIF 2 alpha isolated in the nonphosphorylated state . ^^^ This is in contrast with the studies in rabbit reticulocyte lysates , in which arrested protein synthesis was correlated with a relative increase in the extent of phosphorylation of eIF 2 alpha . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Evidence for a second phosphorylation site on eIF 2 alpha from rabbit reticulocytes . ^^^ Ser 51 in the NH 2 terminal sequence of the alpha subunit of eukaryotic peptide initiation factor 2 ( eIF 2 ) has been identified as a second phosphorylation site for the heme controlled eIF 2 alpha kinase from rabbit reticulocytes . ^^^ A synthetic peptide corresponding to eIF 2 alpha ( 41 54 ) is phosphorylated only in Ser 51 by the eIF 2 alpha kinase . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The amino terminal of eIF 2 alpha from amino acid positions 1 to 23 inclusive was determined . ^^^ Additionally , the partial amino acid sequence data permitted the designation of synthetic gene probes as well as the identification of eIF 2 alpha and gamma cDNA and / or genomic clones . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
An isolation procedure for the reticulocyte heme controlled alpha subunit of eukaryotic translational initiation factor 2 ( eIF 2 alpha ) kinase is described which yields different fractions with kinase activity . ^^^ Isolated alpha or beta spectrin subunits as well as the separated homogeneous Mr 90 , 000 peptide cause an increase in the initial rate of eIF 2 alpha phosphorylation that is related to a decrease in Km with little or no effect on Vmax for the phosphorylation reaction . ^^^ Fractionation of highly purified eIF 2 alpha kinase preparations using affinity chromatography on monoclonal anti spectrin antibodies has separated eIF 2 alpha kinase activity from the Mr 100 , 000 phosphopeptide which copurifies with the kinase during all other purification steps . ^^^ A Mr 95 , 000 peptide , detectable only by photoaffinity labeling with 8 azido [ alpha 32P ] ATP , is shown to be distinct from the Mr 100 , 000 phosphopeptide and appears to be the catalytic subunit of the eIF 2 alpha kinase . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The rabbit reticulocyte heme regulated eIF 2 alpha kinase ( HRI ) utilizes adenosine 5 ' 0 ( 3 thiotriphosphate ) ( ATP gamma S ) as a substrate for its autophosphorylation and activation , and for the phosphorylation of eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Recent observations have indicated that eukaryotic initiation factor ( eIF ) 2 and GTP or GDP normally bind to 60 S ribosomal subunits in rabbit reticulocyte lysate and that when eIF 2 alpha is phosphorylated and polypeptide chain initiation is inhibited , eIF 2 10 GDP accumulates on 60 S subunits due to impaired dissociation that is normally mediated by the reversing factor ( eIF 2B ) . ^^^ Current findings now indicate that inhibition due to phosphorylation of eIF 2 alpha is mediated , at least in part , by the inability to dissociate eIF 2 10 GDP from the 60 S subunit of complete initiation complexes . ^^^ These results suggest that eIF 2B must normally promote dissociation of eIF 2 10 GDP from the 60 S subunit of complete initiation complexes before they can elongate but can not when eIF 2 alpha is phosphorylated , resulting in the accumulation of these complexes , some of which dissociate into Met tRNA ( f ) 10 40 S 10 mRNA and 60 S 10 eIF 2 10 GDP . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
To determine whether phosphorylation of eIF 2 alpha is a likely regulatory mechanism in the Ehrlich cell , we have measured the percent of cellular eIF 2 alpha which is phosphorylated in cells exposed to heat shock , 2 deoxyglucose , or amino acid deprivation , conditions which rapidly decrease the concentration of 40 S initiation complexes and inhibit protein synthesis . eIF 2 alpha and eIf 2 alpha ( P ) were separated by isoelectric focusing and were detected by immunoblotting with a monoclonal antibody we developed for this purpose . ^^^ Under the above three inhibitory conditions , phosphorylation of eIF 2 alpha increased rapidly , and this increase correlated in time with the rapid inhibition of protein synthesis . ^^^ This steep curve of inhibition is consistent with a mechanism in which eIF 2 alpha ( P ) saturates and inhibits the guanine nucleotide exchange factor . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The stimulation of protein synthesis observed upon the addition of cAMP to heavy metal ion inhibited lysates correlated with the inhibition of eIF 2 alpha phosphorylation and the restoration of RF activity . ^^^ The partial restoration of protein synthesis observed upon the addition of MgGTP to heavy metal ion inhibited lysates correlated with a partial inhibition of eIF 2 alpha phosphorylation . ^^^ Addition of glucose 6 phosphate was found to have no effect on protein synthesis of eIF 2 alpha phosphorylation under these conditions . ^^^ Antiserum raised to the reticulocyte heme regulated eIF 2 alpha kinase inhibited the phosphorylation of eIF 2 alpha catalyzed by Hg2+ inhibited lysate . ^^^ The data presented here indicate that heavy metal ions inhibit protein chain initiation in hemin supplemented lysates by stimulating the phosphorylation of eIF 2 alpha apparently through the activation of the heme regulated eIF 2 alpha kinase rather than through inhibition of the rate of eIF 2 alpha dephosphorylation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Adenovirus VAI RNA antagonizes the antiviral action of interferon by preventing activation of the interferon induced eIF 2 alpha kinase . ^^^ VAI RNA prevents activation of the interferon induced P1 / eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
On the basis of weight of protein added to a lysate reaction mixture , it has about half the inhibitory activity of highly purified heme regulated eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Inhibition of HeLa cell protein synthesis under heat shock conditions in the absence of initiation factor eIF 2 alpha phosphorylation . ^^^ Using an in vitro translation system derived from heat shocked HeLa cells grown in suspension culture , we were unable to find any evidence implicating eIF 2 alpha phosphorylation in the initial shutoff of translation during the heat shock response . ^^^ These results suggest that the rapid inhibition of protein synthesis observed under heat shock conditions is mediated by a mechanism ( s ) other than eIF 2 alpha phosphorylation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The NH 2 terminal sequence of the alpha and gamma subunits of eukaryotic initiation factor 2 and the phosphorylation site for the heme regulated eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This strongly suggests that influenza virus encodes a gene product that , analogous to the adenoviral VAI RNA , prevents the shutdown of overall protein synthesis caused by an eIF 2 alpha kinase turned on by viral infection . ^^^ Addition of double stranded RNA to the extracts from these cells restored the eIF 2 alpha kinase to a level approaching that seen in extracts from cells infected with dl 331 alone and caused the inhibition of influenza viral mRNA translation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
VAI RNA prevented activation of the interferon induced P1 / eIF 2 alpha kinase . ^^^ In its absence the kinase was activated , eIF 2 alpha was phosphorylated , and translational initiation was inhibited . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The anti HCR IgG also prevents or reverses the phosphorylation of eIF 2 alpha and the reduced binding of Met tRNAf to 40 S ribosomal subunits that accompanies the inhibition of protein synthesis in hemin deficient lysate . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This dissociation reaction was presumably due to loss of interaction of the Co eIF 2A component in Co eIF 2 with the ternary complex ( reversal of Co eIF 2A activity ) as the complex became increasingly sensitive to aurintricarboxylic acid with increasing Mg2+ concentration . ^^^ Such stimulatory activity in each case was strongly inhibited by prior phosphorylation of eIF 2 alpha subunit by heme regulated translational inhibitor . ( 3 ) Ternary complexes preformed using either native and GDP free eIF 2 and excess Co eIF 2A80 in the absence of Mg2+ did not form Met tRNAf 10 40 S 10 AUG complex . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Further , in contrast to cells infected with wild type serotype 2 adenovirus , dl 331 infected cells contain increased eIF 2 alpha kinase activity . ^^^ These results indicate that VA RNAI plays a role in suppressing eIF 2 alpha kinase activity during adenovirus infection of HeLa cells . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The major proteins of polyribosomal informosomes do not coincide in terms of electrophoretic mobility with initiation factors eIF 2 , eIF 2A , eIF 3 , eIF 4A and eIF 4B . ^^^ The major proteins of free informosomes differ in their electrophoretic mobility from initiation factors eIF 2A , eIF 4A and eIF 4B as well as from the alpha and beta subunits of initiation factor eIF 2 . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In lysates inhibited by heme deficiency , phosphorylated eIF 2 alpha can be detected on polyribosomal 60 S subunits early in the initial linear phase of protein synthesis ; after polyribosomal disaggregation and shut off of protein synthesis , phosphorylated eIF 2 alpha accumulates on free 60 S ribosome subunits and on the 60 S subunits of 80 S ribosome couples . ^^^ The phosphorylated eIF 2 alpha associated with the 60 S subunits in heme deficient lysates appears to be present as the binary complex [ eIF 2 ( alpha P ) 10 GDP ] ; the binding of this complex to the 60 S subunit is tight and is not affected by treatment with 25 mM EDTA or by sedimentation in sucrose gradients . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The inhibitor phosphorylated the serine residue of the alpha subunit of eIF 2 ( eIF 2 alpha ) and 1 mol of phosphate was incorporated into 1 mol of eIF 2 alpha by the inhibitor on maximal phosphorylation , even when eIF 2 was pretreated with alkaline phosphatase prior to phosphorylation . ^^^ The 32P labeled eIF 2 alpha was subjected to tryptic digestion and the tryptic digest was analyzed by two dimensional peptide mapping on a cellulose thin layer sheet . ^^^ These findings suggest that one specific serine residue of pig liver eIF 2 alpha was phosphorylated by the NEM treated HCI . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A Mr 90 , 000 polypeptide and eIF 2 alpha were phosphorylated in this extract , but hemin or an antibody which inhibits the protein kinase designated heme controlled repressor reduced this phosphorylation . ^^^ These findings implicated heme controlled repressor as the kinase at least in part responsible for eIF 2 alpha phosphorylation . ^^^ Furthermore , the initial inhibition of protein synthesis and eIF 2 alpha phosphorylation after heat shock were reduced by adding hemin to intact HeLa cells . ^^^ The binding of Met tRNAf to 40 S ribosomal subunits was inhibited by about 50 % in extracts prepared from cells heat shocked for 40 min , and eIF 2 alpha phosphorylation was increased in these cells . ^^^ These results suggest that heme controlled repressor is activated in heat shocked cells and that eIF 2 alpha phosphorylation limits mRNA translation even after partial recovery of protein synthesis . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Incubation of neuroblastoma cell lysate in the presence of [ gamma 32P ] ATP results in the phosphorylation of a protein of Mr 36 000 , migrating on SDS polyacrylamide gels to the position of eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The dsRNA dependent P1 / eIF 2 alpha kinase was purified at least 1 , 500 fold from interferon treated cells ; the kinase activity that catalyzed the phosphorylation of eIF 2 alpha copurified with protein P 1 . ^^^ The yield of P1 / eIF 2 alpha protein kinase activity obtained following purification from cells treated with interferon was about 5 10 times greater than the yield from an equivalent number of untreated cells . ^^^ N Ethylmaleimide , ethylenediaminetetraacetic acid , AMP , pyrophosphate , spermine , spermidine , and high concentrations of potassium inhibited both P 1 and eIF 2 alpha phosphorylation by the purified kinase , whereas ethylene glycol bis ( beta aminoethyl ether ) N , N , N ' , N ' tetraacetic acid and phenanthroline did not significantly affect the phosphorylation of either protein P 1 or eIF 2 alpha . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A novel approach to the isolation of rabbit reticulocyte haem controlled eIF 2 alpha protein kinase . ^^^ A new strategy for the purification of rabbit reticulocyte haem controlled eIF 2 alpha kinase is described , based on the fact that this kinase can be self phosphorylated in several sites . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
After eIF 2 alpha is phosphorylated , the mRNA becomes associated with 48S complexes consisting of a 40S ribosomal subunit , eIF 2 ( alpha P ) , GDP and Met tRNAf . ^^^ One of the eIF 2 alpha kinases is activated by low concentrations of double stranded RNA ( dsRNA ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation studies showed that both helenalin and bis ( helenalinyl ) malonate were equally effective at activating eIF 2 alpha kinase and indirectly causing phosphorylation of eIF 2 . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
On the other hand , it is shown that phosphorylation of eIF 2 by the hemin regulated inhibitor ( HRI ) abolishes the recycling of eIF 2 , by the formation of another stable complex comprising eIF 2 alpha P , GDP and eRF . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The induction of phosphorylation of both protein P 1 and protein synthesis initiation factor eIF 2 alpha and the inhibition of virus replication were examined in mouse L 929 fibroblasts treated with either natural mouse or individual cloned human interferons ( IFN ) . ^^^ Two other cloned human IFNs , alpha A and alpha D / A , were poor inducers of both the antiviral state and the phosphorylation of P 1 and eIF 2 alpha in mouse L 929 cells . ^^^ The ability of individual human IFN alpha subspecies to induce P 1 and eIF 2 alpha phosphorylation in mouse L 929 cells correlated with their ability to induce an antiviral state . ^^^ Furthermore , the detailed kinetics of induction , in mouse L 929 cells , of P 1 and eIF 2 alpha phosphorylation and of the antiviral state by the heterologous cloned human IFN alpha A / D were equivalent to the kinetics of induction by the homologous natural mouse L 929 IFN . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The decay of the IFN induced protein kinase which catalyzes the phosphorylation of endogenous protein P 1 and purified initiation factor eIF 2 alpha correlated with the decay of the antiviral state . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In the interferon treated mouse L cell system , both double stranded RNAs stimulated kinase activity , leading to phosphorylation of protein P 1 and eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) , but only ( 1 ) n 10 ( C ) n activated the ( 2 ' 5 ' ) oligoadenylate synthetase . ^^^ Both ( A ) n 10 ( dUfl ) n and ( 1 ) n 10 ( C ) n also activated the rabbit reticulocyte kinase to phosphorylate protein P 1 and eIF 2 alpha , but , in contrast to mouse L cell systems , both ( A ) n 10 ( dUfl ) n and ( 1 ) n 10 ( C ) n were potent inhibitors of translation in reticulocyte lysates . ^^^ These results indicate that protein P 1 and eIF 2 alpha phosphorylation are not sufficient to cause inhibition of protein synthesis in interferon treated mouse L cell extracts . ^^^ They further suggest that protein synthesis inhibition by ( 1 ) n 10 ( C ) n in extracts of interferon treated L cells correlates better with activation of ( 2 ' 5 ' ) oligoadenylate synthetase than with activation of the protein P 1 and eIF 2 alpha kinase . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The experimental data reviewed in this paper suggest that the inhibition of viral polypeptide chain initiation in IFN treated cells involves the phosphorylation of eIF 2 alpha and intermediate factors ( 65K and 67K ribosomal proteins ) by an IFN induced dsRNA dependent ribosomal kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
However , high concentrations of dsRNA ( greater than 100 micrograms / ml ) drastically reduced the phosphorylation of both P 1 and eIF 2 alpha . ^^^ Neither P 1 nor eIF 2 alpha phosphorylation was affected by either pA ( 2 ' p5 ' A ) 2 or pppA ( 2 ' p5 ' A ) 3 . 3 ) The translation of reovirus mRNA in vitro was inhibited by the addition of either low concentrations of dsRNA or pppA ( 2 ' p5 ' A ) 3 . ^^^ Under conditions where the pppA ( 2 ' p5 ' A ) 3mediated degradation of reovirus mRNA was blocked , the translation of reovirus mRNA was still inhibited by low but not by high concentrations of dsRNA in a manner that correlated with the activation of P 1 and eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Specific phosphorylation of eukaryotic initiation factor 2 alpha , eIF 2 alpha , by bovine adrenocortical cyclic nucleotide independent protein kinase , PK 380 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Mechanism of interferon action : eIF 2 alpha phosphatase in interferon treated mouse fibroblasts is double stranded RNA independent . ^^^ These results indicate that the enhanced phosphorylation of eIF 2 alpha observed in IFN treated systems in the presence of double stranded RNA ( dsRNA ) is indeed caused by an activation of a protein kinase rather than to an inhibition of a phosphoprotein phosphatase by the dsRNA . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Of interest was the observation that muscle 1 2 appeared to regulate protein synthesis in reticulocyte lysates by inhibiting an eIF 2 alpha phosphatase with type 1 properties . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
To understand the nature of the molecular lesion in eIF 2 alpha phosphorylation we used a system of pure components in which the rate of exchange of eIF 2 bound [ 3H ] GDP with unlabeled GDP ( via the reaction eIF 2 GDP + GEF in equilibrium eIF 2 GEF + GDP ) was measured by using mixtures of eIF 2 ( alpha P ) 10 [ eH ] GDP and eIF 2 10 [ 3H ] GDP in different proportions at constant concentration of eIF 2 10 GEF . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Identical or closely located amino acids in the eIF 2 alpha subunit are phosphorylated by the chondrocyte kinase ( s ) and the rabbit reticulocyte hemin regulated kinase as indicated by comparative peptide fragment analysis of [ 32P ] labeled alpha subunits . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Neither wheat germ eIF 2 nor Euglena eIF 2A can bind fMet tRNA efficiently to Euglena chloroplast or E . coli 30 S subunits although both are active with wheat germ 40 S ribosomal subunits . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Increased phosphorylation of protein synthesis initiation factor eIF 2 alpha in interferon treated , reovirus infected mouse L 929 fibroblasts in vitro and in vivo . ^^^ The effect of interferon ( IFN ) treatment and virus infection on the phosphorylation both in vitro and in vivo of the alpha subunit of protein synthesis initiation factor eIF 2 ( eIF 2 alpha ) was examined in mouse fibroblast L 929 cells . ^^^ The [ gamma 32P ] ATP mediated in vitro phosphorylation of eIF 2 alpha catalyzed by cell free extracts prepared from IFN treated , uninfected cells was dependent upon exogenously added double stranded RNA ( dsRNA ) . ^^^ However , the dsRNA requirement for eIF 2 alpha phosphorylation in vitro was eliminated by prior infection of cells with reovirus Dearing strain virions but not with defective top component particles . ^^^ The enhanced phosphorylation in vitro of eIF 2 alpha and ribosome associated protein P 1 depended in a similar manner upon the multiplicity of virus infection . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have studied the relationship between cell growth and phosphorylation of the 67K protein ( designated 3T3 dsRNA dependent eIF 2 alpha kinase ) . ^^^ The phosphorylation of dsI and the phosphorylation of a 38K protein identified as the alpha subunit ( 38K ) of 3T3 eIF 2 ( eIF 2 alpha ) occurred concomitantly ; the levels of these phosphorylations confluent and thereafter decreased markedly . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of initiation factor eIF 2 alpha , binding of mRNA to 48 S complexes , and its reutilization in initiation of protein synthesis . ^^^ Therefore , the formation of this complex was attributed to the phosphorylation of eIF 2 alpha by a dsRNA activated protein kinase . ^^^ The shift of mRNA from 48 S to 80 S complexes was also observed when the eIF 2 alpha kinase activity was inhibited by the addition of 2 aminopurine . ^^^ This finding indicated that eIF 2 alpha phosphorylation could be in part responsible for limiting the duration of protein synthesis in mammalian cell free systems . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Heme regulated protein synthesis inhibitor , HRI , phosphorylates the alpha subunit of eIF 2 and thus inhibits ternary complex formation as Co eIF 2 does not displace GDP from eIF 2 alpha ( P ) 10 GDP . ^^^ Based on these observations , we have suggested ( a ) RF provides the unphosphorylated alpha subunit to eIF 2 alpha ( P ) 10 GDP and restores eIF 2 activity . ^^^ In the presence of HRI and ATP , Co eIF 2 but does not displace GDP from eIF 2 alpha ( P ) 10 GDP . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Control of protein synthesis in human reticulocytes by heme regulated and double stranded RNA dependent eIF 2 alpha kinases . ^^^ These kinases inhibit protein synthesis by phosphorylating the 38 , 000 daltons ( 38K ) subunit of the initiation factor eIF 2 ( eIF 2 alpha ) . ^^^ Human reticulocyte enriched lysates contain the hemin regulated and dsRNA dependent protein kinases which inhibit protein synthesis and which phosphorylate rabbit eIF 2 alpha . ^^^ An endogenous 38K polypeptide which co migrates with rabbit eIF 2 alpha is also phosphorylated . ^^^ In contrast , human mature erythrocytes contain little or no heme regulated or dsRNA dependent eIF 2 alpha kinase activities which are inhibitory of protein synthesis . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Effects of glucose 6 phosphate and hemin on activation of heme regulated eIF 2 alpha kinase in gel filtered reticulocyte lysates . ^^^ In heme deficient reticulocyte lysates , protein synthesis initiation is inhibited due to the activation of a heme regulated protein kinase which blocks protein synthesis by the specific phosphorylation of the alpha sub unit of eukaryotic initiation factor 2 ( eIF 2 alpha ) . ^^^ The omission of either component gives rise to inhibitions which are characterized by the activation of heme regulated eIF 2 alpha kinase and the concomitant phosphorylation of both endogenous heme regulated eIF 2 alpha kinase and endogenous eIF 2 alpha , indicating that glucose 6 P is involved in the regulation of heme regulated eIF 2 alpha kinase . ^^^ In support of this , we find ( a ) that gel filtered lysates incubated with hemin but depleted of glucose 6 P produce sufficient heme regulated eIF 2 alpha kinase to inhibit protein synthesis when mixed with normal hemin supplemented lysates ; ( b ) the inhibitions of protein synthesis produced by heme regulated eIF 2 alpha kinase generated either in glucose 6 P depleted lysates or heme deficient lysates are reversed by added eIF 2 ; and ( c ) the eIF 2 alpha kinase activities formed in the absence of either hemin or glucose 6 P are both neutralized by an anti heme regulated eIF 2 alpha kinase antiserum . ^^^ We conclude that the physiological activation of heme regulated eIF 2 alpha kinase is controlled by both hemin and glucose 6 P . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The effect of Mn2+ is mediated at the level of activation and eIF 2 alpha kinase activity of these two regulatory protein kinases . ^^^ Specifically , Mn2+ inhibits activation of the hemin controlled translational repressor in the absence of hemin and the phosphorylation of eIF 2 alpha by pre activated translational repressor . ^^^ In contrast , the phosphorylation of eIF 2 alpha by the double stranded RNA activated inhibitor is not suppressed by Mn2+ , and the activation and autophosphorylation of this inhibitor is enhanced by Mn2+ . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The inhibitory component was characterized as dsRNA by several criteria including ( 1 ) the ability to activate the lysate dsRNA dependent eIF 2 alpha kinase ( dsI ) ; ( 2 ) the prevention of both dsI activation and inhibition of protein synthesis by high levels of dsRNA or cAMP ; ( 3 ) the reversal of inhibition by eIF 2 ; and ( 4 ) the inability to inhibit protein synthesis in wheat germ extracts which lack latent dsI . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
When lysate samples were pulsed with [ gamma 32P ] ATP at 15 min of incubation , the addition of the supernatant factor at zero time or after 7 min was associated with preventing or reversing the phosphorylation of eIF 2 alpha . ^^^ In contrast , another soluble reticulocyte protein termed reversing factor can be separated from the supernatant factor on phosphocellulose , partly overcomes the effect of the irreversible translational repressor , and is associated with increased phosphorylation of eIF 2 alpha . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Stimulation of ternary complex formation and dissociation have similar ( a ) pH optima , ( b ) metal ion specificity , and ( c ) sensitivity to phosphorylation of the eIF 2 alpha subunit . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In heme deficient reticulocytes and their lysates , a heme regulated inhibitor of protein synthesis is activated ; this inhibitor is a cyclic AMP independent protein kinase that specifically phosphorylates the alpha subunit of the eukaryotic initiation factor 2 ( eIF 2 alpha ) . ^^^ The phosphorylation of HRI , its eIF 2 alpha kinase activity , and its ability to inhibit protein synthesis are diminished by hemin ( 5 microM ) and increased by N ethylmaleimide ( MalNEt ) . ^^^ These findings demonstrate a correlation of the phosphorylation of HRI , its eIF 2 alpha kinase activity , and its inhibition of protein synthesis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Their virtually identical NaDodSO4 / polyacrylamide gel electrophoretic patterns show , in addition to the eIF 2 alpha ( 38 , 000 ) , beta ( 52 , 000 ) , and gamma ( 54 , 000 ) bands , peptide bands at approximately 80 , 65 , 57 , 40 , and 32 kilodaltons . ^^^ Phosphorylation of the eIF 2 alpha subunit by preincubation with eIF 2 alpha kinase and ATP , which virtually blocks eIF 2 ESP interaction , results in only partial blocking of the interaction with RF . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Under nondenaturing conditions the 4 , 000 dalton peptide remains bound to the modified eIF 2 and still can be phosphorylated by the heme controlled eIF 2 alpha kinase from reticulocytes . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Studies in intact rabbit reticulocytes and reticulocyte lysates provide further evidence of a functional role for the phosphorylation of eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) in the regulation of initiation of protein synthesis in eukaryotic cells . ^^^ In intact reticulocytes treated with isonicotinic acid hydrazide to inhibit heme synthesis , the phosphorylation of eIF 2 alpha was significantly greater than in control cells . ^^^ In heme deficient reticulocyte lysates and in lysates treated with double stranded RNA , significant phosphorylation of eIF 2 alpha occurred prior to the onset of inhibition of protein synthesis ; a large proportion , however , of the total eIF 2 alpha remained unphosphorylated . ^^^ These findings indicate that a modest concentration of phosphorylated eIF 2 alpha can suffice to inhibit initiation , and they suggest that one of the factors with which eIF 2 must interact may be rate limiting , especially when eIF 2 alpha is phosphorylated . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The eIF 2 alpha ( P ) thus formed is not recognized by two eIF 2 ancillary factors , Co eIF 2B ( which promotes the dissociation of the ternary complex at high Mg2+ ) and Co eIF 2C ( which reverses the inhibition of ternary complex formation ) , and thus , is presumably inactive in peptide chain initiation . ^^^ An active RF preparation contains Co eIF 2B and Co eIF 2C activities , and these two activities in RF preparation are not inhibited by HRI and ATP i . e . , eIF 2 alpha ( P ) is recognized . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the eIF 2 alpha subunit does not modify the basic properties of the factor but prevents its interaction with a stimulating protein ( SP ) required for binary complex formation at low , physiological concentrations of eIF 2 and Mg 2+ . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Polyamines putrescine , spermidine , and spermine specifically inhibit the PK 380 catalyzed phosphorylation of eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) . ^^^ Since te PK 380 dependent phosphorylation of eIF 2 alpha inhibits the initiation or protein synthesis , the possibility exists that the polyamines enhance protein synthesis by inhibiting the phosphorylation of eIF 2 alpha by PK 380 . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The NEM treated HCI was phosphorylated to an almost constant extent at 20 to 300 mM K+ , but the phosphorylation of eIF 2 alpha by the inhibitor decreased with increasing concentration of KOAc . ^^^ In the light of these data , a possible relationship between the phosphorylation of the inhibitor or eIF 2 alpha and the inhibition of globin synthesis by the inhibitor is discussed . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Also , in partial reactions , eIF 2 alpha ( P ) formed by phosphorylation of eIF 2 using dsI and ATP , is not recognized by two eIF 2 ancillary factors , Co eIF 2B and Co eIF 2C . ^^^ A . 76 , 5076 5079 ) and suggest that dsI , like the heme regulated eIF 2 kinase phosphorylates eIF 2 and eIF 2 alpha ( P ) thus formed , in both cases , is not recognized by Co eIF 2B and Co eIF 2C , and is inactive in some step ( s ) of Met tRNAf . 40 S initiation complex formation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Hemin was compared with other porphyrins for the ability to sustain protein synthesis in reticulocyte lysates and to inhibit the phosphorylation of the alpha subunit of initiation factor 2 ( eIF 2 alpha ) . ^^^ All of the porphyrins and metalloporphyrins tested were observed to inhibit phosphorylation of eIF 2 alpha by highly purified hemin controlled repressor , although at different concentrations . ^^^ Phosphorylation of eIF 2 alpha was examined in reticulocyte lysates . ^^^ Both hemin and protoporphyrin 9 inhibited phosphorylation of eIF 2 alpha in the lysate during this period ; however , hemin sustained protein synthesis whereas protoporphyrin 9 did not . ^^^
Interacting proteins: P20042 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 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the small subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) impairs protein synthesis in mammalian systems . ^^^ Previous reports indicate that one of the wheat germ eIF 2 subunits , the p 40 41 doublet , is phosphorylated by heterologous eIF 2 alpha kinases . ^^^ While heme regulated eIF 2 alpha kinase from reticulocyte lysates does not inhibit wheat germ protein synthesis , CKII and NEM are found to be inhibitory . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
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: P20042 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: P20042 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: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
Characterization of an antisense Inr element in the eIF 2 alpha gene . ^^^ We recently discovered an opposing initiator promoter ( Inr ) downstream of the sense promoter region of the eIF 2 alpha gene ( Silverman , T . , Noguchi , M . , and Safer , B . ( 1992 ) J . ^^^ Sense transcription of the eIF 2 alpha gene proceeds from left to right to generate alpha mRNA ; antisense transcription proceeds from right to left to generate RNA , having a sequence complementary to eIF 2 alpha mRNA . ^^^ A model for the regulation of eIF 2 alpha expression involving the rapid degradation of dsRNA generated by the relative activities of the two overlapping and opposing promoters is proposed . . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
Subsequent analyses of the IFN induced antiviral pathways in 10 infected cells demonstrated that the K3L gene product does not contribute to the previously identified specific kinase inhibitory factor ( SKIF ) activity but does reduce the level of phosphorylated eIF 2 alpha in 10 infected cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This would explain why mutations in eIF 3 mimic eIF 2 alpha phosphorylation in allowing ribosomes to bypass the uORFs and reinitiate at GCN 4 . ^^^
Interacting proteins: P20042 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 . ^^^ Although phosphorylation of eIF 2 alpha interferes with protein translation , sufficient VCAM 1 mRNA translation occurs in response to poly ( 1 ) . poly ( C ) to yield VCAM 1 protein levels that are similar to levels that are induced by IL 1 beta . ^^^ This suggests that the higher , sustained VCAM 1 mRNA levels that occur in response to incubation with poly ( 1 ) . poly ( C ) compensate for the partial translational block resulting from increased eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
GCN 20 , a novel ATP binding cassette protein , and GCN 1 reside in a complex that mediates activation of the eIF 2 alpha kinase GCN 2 in amino acid starved cells . ^^^ We isolated a null mutation in a previously unidentified gene , GCN 20 , that suppresses the growth inhibitory effect of eIF 2 alpha hyperphosphorylation catalyzed by mutationally activated forms of GCN 2 . ^^^ The deletion of GCN 20 in otherwise wild type strains impairs derepression of GCN 4 translation and reduces the level of eIF 2 alpha phosphorylation in vivo , showing that GCN 20 is a positive effector of GCN 2 kinase function . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Calcium depletion from the endoplasmic reticulum inhibits protein synthesis and correlates with increased phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) by a mechanism that does not require ongoing protein synthesis . ^^^ 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 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The histidyl tRNA synthetase related sequence in the eIF 2 alpha protein kinase GCN 2 interacts with tRNA and is required for activation in response to starvation for different amino acids . ^^^
Interacting proteins: P20042 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 . ^^^ Furthermore , expression of a mutant form of eIF 2 alpha , which can not be phosphorylated on Ser 51 also caused malignant transformation of NIH 3T3 cells . ^^^ 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: P20042 and P05198	Pubmed	SVM Score :0.0
This cDNA sequence is highly similar to a rat protein , termed p 67 , which was identified as an inhibitor of phosphorylation of initiation factor eIF 2 alpha and was previously predicted to be a metallopeptidase based on limited sequence homology . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The phosphorylation state of eIF 2 alpha , as determined by isoelectric focusing followed by protein immunoblotting , in the same subcellular fractions , did not reveal the presence of the phosphorylated form in any of the fractions studied . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Regulation of protein synthesis by heme regulated eIF 2 alpha kinase . ^^^ Protein synthesis is regulated by the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) in a variety of cells . ^^^ 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: P20042 and P05198	Pubmed	SVM Score :0.0
The eIF 2 alpha kinases : regulators of protein synthesis in starvation and stress . ^^^ The yeast eIF 2 alpha kinase GCN 2 is stimulated by deprivation for amino acids or purines . ^^^ HRI is an eIF 2 alpha kinase that is activated in rabbit reticulocytes by heme deprivation and stress conditions that elicit the heat shock response . ^^^ The eIF 2 alpha kinase DAI is activated by double stranded RNA during viral infections and is an important component of the interferon response . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The highly acidic C terminal region of the yeast initiation factor subunit 2 alpha ( eIF 2 alpha ) contains casein kinase phosphorylation sites and is essential for maintaining normal regulation of GCN 4 . ^^^ However , in the present paper we show that this is not the only site of phosphorylation in yeast eIF 2 alpha . ^^^ We report the preparation of recombinant yeast eIF 2 alpha from Escherichia coli and its use in in vitro phosphorylation studies . ^^^ Mammalian HCR and dsI are shown to phosphorylate specifically Ser 51 of yeast eIF 2 alpha , whereas extracts from yeast cells do not . ^^^ A triple Ser > Ala mutant form of yeast eIF 2 alpha was found to be no longer phosphorylated by either of the yeast ( or mammalian ) casein kinase activities in vitro . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Structural requirements for double stranded RNA binding , dimerization , and activation of the human eIF 2 alpha kinase DAI in Saccharomyces cerevisiae . ^^^ The protein kinase DAI is activated upon viral infection of mammalian cells and inhibits protein synthesis by phosphorylation of the alpha subunit of translation initiation factor 2 ( eIF 2 alpha ) . ^^^ High level expression of DAI in Saccharomyces cerevisiae cells is lethal because of hyperphosphorylation of eIF 2 alpha ; at lower levels , DAI can functionally replace the protein kinase GCN 2 and stimulate translation of GCN 4 mRNA . ^^^ We suggest that large structural alterations in the kinase domain impair an interaction between the two protomers in a DAI dimer that is necessary for activation by dsRNA or for catalysis of eIF 2 alpha phosphorylation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Perturbation of endoplasmic reticular ( ER ) function signals increased expression of the gene encoding the ER resident chaperone Grp78 / BiP and rapid suppression of translational initiation accompanied by phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 ) . eIF 2 alpha phosphorylation and grp 78 mRNA induction were measured in GH 3 pituitary cells subjected to varied degrees of ER stress to ascertain whether activation of an eIF 2 alpha kinase is involved in both events . grp 78 mRNA was induced at low concentrations of ionomycin and dithiothreitol that did not provoke eIF 2 alpha phosphorylation or inhibition of amino acid incorporation . ^^^ Mobilization of the bulk of cell associated Ca2+ and the induction of grp 78 mRNA occurred at comparable low concentrations of ionomycin , whereas phosphorylation of eIF 2 alpha and inhibition of protein synthesis required higher ionophore concentrations . ^^^ Pretreatment for 1 h with cycloheximide suppressed grp 78 mRNA induction and eIF 2 alpha phosphorylation in response to either stressor . ^^^ Prolonged ( 17 h ) cycloheximide blockade increased eIF 2 alpha phosphorylation without inducing grp 78 mRNA . ^^^ Upon release from the blockade , grp 78 mRNA was induced and eIF 2 alpha was dephosphorylated . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The two ' new ' observations are the ability of a 67 kDa protein to influence the phosphorylation state of eIF 2 alpha and a new mechanistic interpretation of the utilization of the mRNA specific factors ( eIF 4A , eIF 4B , eIF 4F ) which would suggest that eIF 4A may not bind to mRNA except as a subunit of eIF 4F . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The gene for eIF 2 alpha has been best characterized , and mechanisms that provide for the coordinated synthesis of eIF 2 subunits are emerging . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Inhibition of protein synthesis by the heme controlled eIF 2 alpha kinase leads to the appearance of mRNA containing 48S complexes that contain eIF 4E but lack methionyl tRNA ( f ) . ^^^ Phosphorylation of the initiation factor eIF 2 by the heme regulated eIF 2 alpha kinase ( HCR ) results in pronounced inhibition of protein synthesis and of binding of Met tRNA ( f ) to 40S subunits in reticulocyte lysates . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Depletion of ER Ca2+ stores was found to signal the activation of a specific eIF 2 alpha kinase . ^^^ Analysis of extracts derived from cultured cells that had been pretreated with Ca2+ ionophore A 23187 or thapsigargin revealed a 2 3 fold increase in eIF 2 alpha kinase activity without detectable changes in eIF 2 alpha phosphatase activity . ^^^ 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: P20042 and P05198	Pubmed	SVM Score :0.0
Heat shock effects on phosphorylation of protein synthesis initiation factor proteins eIF 4E and eIF 2 alpha in Drosophila . ^^^ In these investigations we have carried out a parallel analysis of Drosophila , focusing on eIF 4E and eIF 2 alpha . eIF 4E plus associated proteins was purified from lysates by m7GTP Sepharose chromatography . ^^^ Drosophila eIF 2 alpha has been identified by in vitro translation of T 7 RNA polymerase transcribed mRNA , and immunoblotting with anti Drosophila eIF 2 alpha antiserum . 32P labeling analysis ( unfractionated cell lysates and immunoprecipitates ) detects phosphorylated eIF 2 alpha , whose amount increases approximately 2 3 fold upon heat shock . ^^^ Immunoblotting analysis of two dimensional gel resolved proteins to determine the mass fraction of eIF 2 alpha phosphorylated detects a single eIF 2 alpha spot in both normal temperature and heat shocked cells , indicating less than 5 % phosphorylation after and before heat shock . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In contrast , the inhibition of initiation that occurs in skeletal muscle deprived of insulin is not due to a change in the phosphorylation state of eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of eIF 2 alpha leads to inhibition of eIF 2B . ^^^ However , this subunit may confer sensitivity to eIF 2 alpha phosphorylation . cDNAs encoding the alpha , beta , delta and epsilon subunits have been cloned from mammalian sources . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have recently demonstrated that hemin regulates eIF 2 alpha kinase activity by promoting formation of the inactive heterodimer between HCI and the 90 kDa heat shock protein ( hsp 90 ) . ^^^ Thus , the synthetic peptide RRREEETEEE , which is a specific substrate for CK 2 , acts as a competitive inhibitor of HCI and hsp 90 phosphorylation and , at the same time , inhibits the activation of HCI , whereas a synthetic peptide which corresponds to residues 45 59 of the alpha subunit of eIF 2 , including the Ser 51 phosphorylated by HCI , only inhibits competitively the phosphorylation of eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Cloning and characterization of cDNA encoding rat hemin sensitive initiation factor 2 alpha ( eIF 2 alpha ) kinase . ^^^ Reticulocytes contain an eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) kinase that is negatively regulated by hemin . ^^^ As reported herein , we have cloned and characterized the cDNA encoding an eIF 2 alpha kinase from rat brain . ^^^ We have expressed the rat brain cDNA in Escherichia coli and have demonstrated that the recombinant enzyme is a hemin sensitive eIF 2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Erythroid expression of the heme regulated eIF 2 alpha kinase . ^^^ The role of heme regulated eIF 2 alpha kinase ( HRI ) in the regulation of protein synthesis in rabbit reticulocytes is well documented . ^^^ Inhibitors of protein synthesis with properties similar to those of HRI have been described in some nonerythroid cell types , but it has not yet been determined whether these eIF 2 alpha kinase activities are mediated by HRI or one or more as yet uncharacterized kinases . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have purified a soluble rabbit reticulocyte protein , previously termed the supernatant factor , that reverses the inhibition of protein synthesis in hemin deficient lysate by promoting the inactivation of the hemin controlled eIF 2 alpha kinase ( HCR ) mediating the effect of hemin deficiency . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Inhibition of protein synthesis in insect cells by baculovirus expressed heme regulated eIF 2 alpha kinase . ^^^ To study further the regulation of the heme regulated eIF 2 alpha kinase ( HRI ) , we have produced functional wild type HRI using the baculovirus expression system . ^^^ It is active both as an autokinase and an eIF 2 alpha kinase . ^^^ Coexpression of the wild type HRI with the inactive K199R HRI , S51A eIF 2 alpha , or interleukin 1 beta ( IL 1 beta ) results in diminished expression of these proteins . ^^^ Furthermore , expression of wild type HRI is increased by coexpression with the nonphosphorylatable S51A eIF 2 alpha or by the addition of hemin , which inhibits HRI activity . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
After heating , eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) becomes phosphorylated which prevents the binding of Met tRNA to the 40s ribosomal subunit inhibiting initiation of translation . ^^^ Here we have examined the effects of increased intracellular levels of hsp 70 protein on translation and eIF 2 alpha phosphorylation using rat fibroblasts stably transfected with a cloned human hsp 70 gene . ^^^ Utilizing slab gel isoelectric focusing coupled with immunoblotting we demonstrate that 45 degrees C heat shock leads to a rapid 4 5 fold increase in eIF 2 alpha phosphorylation , with little difference seen between control cells and hsp 70 transfected cells . ^^^ However , dephosphorylation of eIF 2 alpha occurs faster in the hsp 70 transfected cells . ^^^ These results suggest that hsp 70 may play a role in facilitating the dephosphorylation of eIF 2 alpha as well as reversing the inhibition of translation following heat shock . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) is one of the best characterized mechanisms for down regulating total protein synthesis in mammalian cells in response to various stress conditions . ^^^ Recent work indicates that regulation of the GCN 4 gene of Saccharomyces cerevisiae by amino acid availability represents a gene specific case of translational control by phosphorylation of eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Increased phosphorylation of eIF 2 alpha ( 5 fold ) and inhibition of eIF 2B activity ( 50 % ) occur in intact GH 3 cells exposed to these agents for 15 min ( Prostko et al . ^^^ Alterations in eIF 2 alpha phosphorylation and translational activity in response to EGTA were reversed by addition of Ca2+ in excess of chelator while responses to DTT were reversible by washing . ^^^ Exposure for 3 h to either A 23187 or DTT , previously shown to induce transcription dependent translational recovery , resulted in dephosphorylation of eIF 2 alpha in a manner blocked by actinomycin D . ^^^ Phosphorylation of eIF 2 alpha in response to A 23187 or DTT was not prevented by conventional inhibitors of translation including cycloheximide , pactamycin , puromycin , or verrucarin . ^^^ Prolonged inhibition of protein synthesis to deplete the ER of substrates for protein processing resulted in increased eIF 2 alpha phosphorylation , decreased eIF 2B activity , and reduced monosome content that were indicative of time dependent blockade ; these inhibitors did not abolish polysomal content . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Multicopy tRNA genes functionally suppress mutations in yeast eIF 2 alpha kinase GCN 2 : evidence for separate pathways coupling GCN 4 expression to unchanged tRNA . ^^^ In contrast to the wild type tRNA ( His ) genes , the mutant tRNA ( Val ) gene efficiently suppressed a gcn 2 deletion , and this suppression was independent of the phosphorylation site on eIF 2 alpha ( Ser 51 ) . ^^^ We propose that the multicopy mutant tRNA ( Val ) construct leads to an accumulation of uncharged tRNA ( Val ) that derepresses GCN 4 translation through a pathway that does not involve GCN 2 or eIF 2 alpha phosphorylation . ^^^ Because the mutant tRNA ( Val ) exacerbated the slow growth phenotype associated with eIF 2 alpha hyperphosphorylation by an activated GCN2c kinase , we suggest that the GCN 2 independent derepression mechanism involves down regulation of eIF 2 activity . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Mechanism of regulation of eIF 2 alpha subunit phosphorylation by dsI and p 67 was studied . ^^^ The results are as follows : ( 1 ) At low dsI concentration , p 67 protected equimolar concentration of eIF 2 . ( 2 ) At high dsI concentration , dsI efficiently phosphorylated eIF 2 alpha subunit even when equimolar concentrations of both p 67 and eIF 2 were present . ^^^ Significantly increased p 67 concentration was necessary to protect eIF 2 alpha subunit at high dsI concentration . ( 3 ) dsI was also phosphorylated as it phosphorylated eIF 2 alpha subunit . p 67 inhibited both eIF 2 alpha subunit and dsI phosphorylation similarly . ( 4 ) Although the [ 32P ] labelled dsI formed during the reaction could be effectively chased upon subsequent addition of excess unlabelled eIF 2 and ATP , the [ 32P ] labelled eIF 2 formed under identical conditions , retained most of the radioactivity . ( 5 ) dsI coimmunoprecipitated with three subunit eIF 2 and p 67 inhibited this coimmunoprecipitation reaction . ^^^ At high concentration , dsI ( P ) can bind to free three subunit eIF 2 and form eIF 2 . dsI ( P ) complex . dsI ( P ) in this complex then transfers its phosphoryl residue to eIF 2 and forms eIF 2 alpha ( P ) in an irreversible reaction . ^^^ Inhibition of eIF 2 alpha subunit phosphorylation by p 67 blocks this phosphorylation cycle and consequent dsI phosphorylation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Expression of mutant eukaryotic initiation factor 2 alpha subunit ( eIF 2 alpha ) reduces inhibition of guanine nucleotide exchange activity of eIF 2B mediated by eIF 2 alpha phosphorylation . ^^^ The inhibition of protein synthesis that occurs upon phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) at serine 51 correlates with reduced guanine nucleotide exchange activity of eIF 2B in vivo and inhibition of eIF 2B activity in vitro , although it is not known if phosphorylation is the cause of the reduced eIF 2B activity in vivo . ^^^ To characterize the importance of eIF 2 alpha phosphorylation in the regulation of eIF 2B activity , we studied the overexpression of mutant eIF 2 alpha subunits in which serine 48 or 51 was replaced by an alanine ( 48A or 51A mutant ) . ^^^ In this study , we show that eIF 2B activity was inhibited in parental CHO cell extracts upon addition of purified reticulocyte heme regulated inhibitor ( HRI ) , an eIF 2 alpha kinase that phosphorylates Ser 51 . ^^^ Preincubation with purified HRI also reduced the eIF 2B activity in extracts from cells overexpressing wild type eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In response to growth , metabolic , and other signals , eukaryotic cells regulate protein biosynthesis through post translational mechanisms which target the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) . ^^^ Previous efforts to study transcriptional mechanisms underlying this regulation identified a novel transcription factor ( alpha Pal ) for the eIF 2 alpha gene . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Casein kinase 2 mediates multiple phosphorylation of Saccharomyces cerevisiae eIF 2 alpha ( encoded by SUI 2 ) , which is required for optimal eIF 2 function in S . cerevisiae . ^^^ Previous studies have demonstrated that the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) , encoded by the SUI 2 gene in the yeast Saccharomyces cerevisiae , is phosphorylated at Ser 51 by the GCN 2 kinase in response to general amino acid control . ^^^ Here we describe that yeast eIF 2 alpha is a constitutively phosphorylated protein species that is multiply phosphorylated by a GCN 2 independent mechanism . 32Pi labeling and isoelectric focusing analysis of a SUI2+ delta gcn 2 strain identifies eIF 2 alpha as radiolabeled and a single isoelectric protein species . ^^^ Treatment of SUI2+ delta gcn 2 strain extracts with phosphatase results in the identification of three additional isoelectric forms of eIF 2 alpha that correspond to the stepwise removal of three phosphates from the protein . ^^^ Mutational analysis of SUI 2 coupled with biochemical analysis of eIF 2 alpha maps the sites to the carboxyl region of SUI 2 that correspond to Ser residues at amino acid positions 292 , 294 , and 301 that compose consensus casein kinase 2 sequences . 32Pi labeling or isoelectric focusing analysis of eIF 2 alpha from conditional casein kinase 2 mutants indicated that phosphorylation of eIF 2 alpha is abolished or dephosphorylated forms of eIF 2 alpha are detected when these strains are grown at the restrictive growth conditions . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We show here that treatment of rat GH 3 pituitary cells with Brefeldin A leads to an inhibition of protein synthesis at the level of peptide chain initiation through a mechanism involving the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
After a 30 min recirculation period , protein synthesis rate , initiation factor 2 ( eIF 2 ) and guanine nucleotide exchange factor ( GEF ) activities , and the level of phosphorylation of the alpha subunit of eIF 2 ( eIF 2 alpha ) were determined in the neocortex region of the brain from sham operated controls and ischaemic animals . ^^^ Since phosphorylated eIF 2 [ eIF 2 ( alpha P ) ] is a powerful inhibitor of GEF , the levels of phosphorylated eIF 2 alpha were determined , and an increase from 7 % phosphorylation in sham control rats to 20 % phosphorylation in 15 min and 29 % phosphorylation in 30 min in ischaemic rats was observed , providing evidence for a tight correlation of phosphorylation of eIF 2 alpha and inhibition of protein synthesis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Mouse erythroleukaemia ( MEL ) cells , which have not been induced into erythroid development , contain a protein kinase ( MKu ) which phosphorylates the alpha subunit of protein synthesis initiation factor 2 ( eIF 2 alpha ) . ^^^ In this paper , we show that this kinase phosphorylates both eIF 2 alpha and a synthetic peptide based on the phosphorylation site in eIF 2 alpha at Ser 51 , the target residue for other eIF 2 alpha kinases . ^^^ MKu has been purified and its properties have been compared with those of the haem controlled repressor eIF 2 alpha kinase ( HCR ) from rabbit reticulocytes . ^^^ This protein undergoes phosphorylation when incubated in the presence of Mg ( 2+ ) ATP , and both this apparent autophosphorylation and the activity of the kinase against eIF 2 alpha are inhibited by the same , low , ( 10 microM ) concentrations of haemin . ^^^
Interacting proteins: P20042 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 . ^^^ In this system , the E3L gene product , and to a lesser extent the K3L gene product , potentiated translation of the reporter gene and inhibited eIF 2 alpha phosphorylation . ^^^ 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 . ^^^ The two inhibitors did not display a synergistic effect on translation or eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A eukaryotic initiation factor 2 ( eIF 2 ) associated 67 kDa polypeptide ( p 67 ) protects the eIF 2 alpha subunit from eIF 2 kinase ( s ) catalyzed phosphorylation , and this promotes protein synthesis in the presence of active eIF 2 kinase ( s ) , [ Datta , B . , et al . ( 1988 ) Proc . ^^^ This report presents the results of studies related to characteristics of p 67 action and the mechanism of p 67 : eIF 2 interaction : ( 1 ) p 67 antibodies inhibited protein synthesis in hemin supplemented rabbit reticulocyte lysates , and such inhibition was reversed by preincubation of the antibodies , specifically with p 67 . ( 2 ) p 67 inhibited HRI and dsI catalyzed phosphorylations of the eIF 2 alpha subunit and histones , but it did not inhibit casein kinase catalyzed phosphorylation of the eIF 2 beta subunit . ( 3 ) p 67 bound specifically to the eIF 2 gamma subunit . p 67 co immunoprecipitated with the eIF 2 subunits when a p67 / eIF 2 mixture was treated with p 67 or eIF 2 subunit antibodies and protein A agarose . ^^^ Preincubation of eIF 2 , with either eIF 2 alpha or beta subunit antibodies , had no effect on p 67 co immunoprecipitation with the eIF 2 subunits . ( 4 ) p 67 : eIF 2 interaction is necessary for p 67 activity to protect the eIF 2 alpha subunit from eIF 2 kinase ( s ) catalyzed phosphorylation . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) in Saccharomyces cerevisiae by the GCN 2 protein kinase stimulates the translation of GCN 4 mRNA . ^^^ The protein kinases heme regulated inhibitor of translation ( HRI ) and double stranded RNA dependent eIF 2 alpha protein kinase ( dsRNA PK ) inhibit initiation of translation in mammalian cells by phosphorylating Ser 51 of eIF 2 alpha . ^^^ We show that HRI and dsRNA PK phosphorylate yeast eIF 2 alpha in vitro and in vivo and functionally substitute for GCN 2 protein to stimulate GCN 4 translation in yeast . ^^^ Phosphorylation of eIF 2 alpha inhibits initiation in mammalian cells by sequestering eIF 2B , the factor required for exchange of GTP for GDP on eIF 2 . ^^^ These results provide further in vivo evidence that phosphorylation of eIF 2 alpha inhibits translation by impairing eIF 2B function and identify GCN 3 as a regulatory subunit of eIF 2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This paper describes the purification of two eIF 2 alpha kinases from Ehrlich cells . ^^^ Unlike the two well characterized eIF 2 alpha kinases , HRI ( heme regulated inhibitor from reticulocytes ) and P 68 ( double stranded RNA dependent kinase found in interferon treated cells ) , the Ehrlich cell kinases do not appear to autophosphorylate . ^^^ The other kinase co purifies with a factor that suppresses inhibition of protein synthesis in reticulocyte lysates by eIF 2 alpha kinases . ^^^
Interacting proteins: P20042 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 . ^^^ Recombinant pK 3 prevents the inhibition of protein synthesis by dsRNA in a cell free translation system from rabbit reticulocytes at levels equal to , or lower than , the level of endogenous eIF 2 alpha . ^^^ In the cell free translation system , pK3r exerts its effects at all dsRNA concentrations tested , by preventing phosphorylation of eIF 2 alpha . ^^^ This tight binding is consistent with a role for pK 3 as a pseudosubstrate for the kinase , and identifies the amino terminal 30 % of eIF 2 alpha as the domain recognized by the eIF 2 alpha specific protein kinases . ^^^ Recombinant pK 3 also prevents activation of the heme sensitive eIF 2 alpha specific protein kinase , eIF 2 alpha PKh , in both cell free translation systems as well as in partially purified preparations . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Denatured proteins inhibit translation in hemin supplemented rabbit reticulocyte lysate by inducing the activation of the heme regulated eIF 2 alpha kinase . ^^^ This stimulation of eIF 2 alpha phosphorylation was inhibited by a monoclonal antibody to HRI , confirming that denatured BSA was causing the activation of HRI . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Mutations in the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 alpha ) that overcome the inhibitory effect of eIF 2 alpha phosphorylation on translation initiation . ^^^ Phosphorylation of eIF 2 alpha in Saccharomyces cerevisiae by the protein kinase GCN 2 leads to inhibition of general translation initiation and a specific increase in translation of GCN 4 mRNA . ^^^ We isolated mutations in the eIF 2 alpha structural gene that do not affect the growth rate of wild type yeast but which suppress the toxic effects of eIF 2 alpha hyperphosphorylation catalyzed by mutationally activated forms of GCN 2 . ^^^ These eIF 2 alpha mutations also impair translational derepression of GCN 4 in strains expressing wild type GCN 2 protein . ^^^ All four mutations alter single amino acids within 40 residues of the phosphorylation site in eIF 2 alpha ; however , three alleles do not decrease the level of eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Purification of eukaryotic initiation factors eIF 2 , eIF 2B and eIF 2 alpha kinase from bovine liver . ^^^ When the alpha subunit of eIF 2 is phosphorylated by an eIF 2 alpha kinase , the phosphorylated eIF 2 alpha ( eIF 2 alpha ( P ) ) binds tightly to eIF 2B and prevents the recycling of eIF 2 . ^^^ Therefore , procedures were developed for the simultaneous purification of eIF 2 , eIF 2B and eIF 2 alpha kinase from kilogram quantities of fresh bovine liver . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In skeletal muscle , neither the eIF 2 content nor the extent of phosphorylation of eIF 2 alpha was altered during sepsis . ^^^ In liver , neither the extent of phosphorylation of eIF 2 alpha nor the activity of eIF 2B was different in rats with a sterile or septic abscess compared with control . ^^^ The relative abundance of eIF 2 alpha mRNA was not increased in either condition compared with control . ^^^ Analysis of the distribution of eIF 2 alpha mRNA from control rats revealed that only approximately 40 % of the message was associated with polysomes . ^^^ Sterile inflammation or sepsis caused a 50 % increase in the proportion of eIF 2 alpha mRNA associated with the polysomes compared with control . ( ABSTRACT TRUNCATED AT 250 WORDS ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Isolation and characterization of the Drosophila melanogaster eIF 2 alpha gene encoding the alpha subunit of translation initiation factor eIF 2 . ^^^ Genomic and cDNA clones encoding the Drosophila melanogaster alpha subunit of translational initiation factor 2 ( eIF 2 alpha ) were isolated . ^^^ The D . melanogaster eIF 2 alpha gene encodes a 341 amino acid ( aa ) protein that shares 57 and 44 % identity to its human and yeast homologues , respectively . ^^^ Analysis of the genomic DNA and cDNA clones indicated that eIF 2 alpha is a single copy gene and its coding region is interrupted by a 260 bp intron . ^^^ The D . melanogaster eIF 2 alpha mRNA is 1350 nt in length and is expressed throughout development . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 alpha ) impairs translation initiation by inhibiting the guanine nucleotide exchange factor for eIF 2 , known as eIF 2B . ^^^ In Saccharomyces cerevisiae , phosphorylation of eIF 2 alpha by the protein kinase GCN 2 specifically stimulates translation of GCN 4 mRNA in addition to reducing general protein synthesis . ^^^ We isolated mutations in several unlinked genes that suppress the growth inhibitory effect of eIF 2 alpha phosphorylation catalyzed by mutationally activated forms of GCN 2 . ^^^ These suppressor mutations , affecting eIF 2 alpha and the essential subunits of eIF 2B encoded by GCD 7 and GCD 2 , do not reduce the level of eIF 2 alpha phosphorylation in cells expressing the activated GCN2c kinase . ^^^ This double GCD 7 mutation also completely suppressed the lethal effect of expressing the mammalian eIF 2 alpha kinase dsRNA PK in yeast cells , showing that the translational machinery had been rendered completely insensitive to phosphorylated eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
While sequencing the region of the AcMNPV genome containing lef 7 , we also found a 215 codon open reading frame ( ORF 215 ) approximately 1 kb downstream of lef 7 with sequence homology to eIF 2 alpha kinases ( e . g . , rabbit eIF 2 alpha and yeast GCN 2 kinase ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
These included a 45 % reduction in total protein synthesis , the induction of heat shock protein ( hsp ) 72 , and increased phosphorylation of the protein synthesis initiation factor eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Increased expression of eukaryotic translation initiation factors eIF 4E and eIF 2 alpha in response to growth induction by c myc . ^^^ Consequently we examined eIF 4E and eIF 2 alpha for evidence of regulation by c myc . ^^^ Expression of eIF 4E and eIF 2 alpha correlated with c myc expression in fibroblasts after growth stimulation . ^^^ In addition , expression of eIF 4E and eIF 2 alpha was increased in myc transformed rat embryo fibroblasts but was not increased in ras transformed cells . ^^^ Transcription rates of eIF 4E and eIF 2 alpha mRNAs were regulated by c myc in cells expressing an estrogen receptor Myc fusion protein . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We show that starvation for purines also stimulates GCN 4 translation by the same mechanism that operates in amino acid starved cells , being dependent on short upstream open reading frames in the GCN 4 mRNA leader , the phosphorylation site in the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 alpha ) , the protein kinase GCN 2 , and translational activators of GCN 4 encoded by GCN 1 and GCN 3 . ^^^ Biochemical experiments show that eIF 2 alpha is phosphorylated in response to purine starvation and that this reaction is completely dependent on GCN 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
After a 30 min exposure at 45 degrees C , the heat shocked cells exhibited several features characteristic of the classical heat shock response including a 45 % reduction in total protein synthesis , the induction of heat shock protein 72 , and an increased phosphorylation of the protein synthesis initiation factor eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The results presented here demonstrate that changes in eIF 2 alpha phosphorylation are not responsible for the effect of diabetes on eIF 2B activity in fast twitch skeletal muscle . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Deletion of either GCD 6 or GCD 7 is lethal , and nonlethal mutations in these genes increase GCN 4 translation in the same fashion described for defects in known subunits of eIF 2 or the GCD complex ; derepression of GCN 4 is dependent on short open reading frames in the GCN 4 mRNA leader and occurs independently of eIF 2 alpha phosphorylation by protein kinase GCN 2 , which is normally required to stimulate GCN 4 translation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 alpha ) by the protein kinase GCN 2 mediates increased translation of the transcriptional activator GCN 4 in amino acid starved yeast cells . ^^^ Inactivation of GCN 1 did not affect the level of eIF 2 alpha phosphorylation when mammalian eIF 2 alpha kinases were expressed in yeast cells in place of GCN 2 , arguing against an involvement of GCN 1 in dephosphorylation of eIF 2 alpha . ^^^ In addition , while GCN 1 is required in vivo for phosphorylation of eIF 2 alpha by GCN 2 , cell extracts from gcn 1 delta strains contained wild type levels of GCN 2 eIF 2 alpha kinase activity . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In mammalian cells , phosphorylation of eIF 2 alpha inhibits the activity of eIF 2B , the GDP GTP exchange factor for eIF 2 . ^^^ This finding suggests that mutations in GCD encoded subunits of the complex derepress GCN 4 translation because they mimic eIF 2 alpha phosphorylation in decreasing eIF 2B activity . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Most notably , phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) on serine residue 51 occurs . ^^^ To identify the importance of phosphorylation in control of protein synthesis , we have evaluated the effects of expression of a mutant eIF 2 alpha which is resistant to phosphorylation . ^^^ Expression of a serine to alanine mutant at residue 51 of eIF 2 alpha partially protected cells from the inhibition of protein synthesis in response to heat treatment . ^^^ These results are consistent with the hypothesis that heat shock inhibition of translation is mediated in part through phosphorylation of eIF 2 alpha . ^^^ Expression of the wild type or mutant eIF 2 alpha did not affect cell survival or induction of hsp 70 mRNA upon heat shock , indicating that although eIF 2 alpha is a heat shock induced protein , its increased synthesis during heat shock does not alter the heat shock response . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Since , in some cases , overexpression of the c myc protein has been shown to increase levels of the translation initiation factors eIF 4E and eIF 2 alpha , which may themselves play a role in malignant conversion , we have also examined the levels of these proteins in BS cells and found them to be either comparable or lower than those in control cell lines . ^^^ These data suggest that if c myc does contribute to the cancer predisposition phenotype in BS then it does not appear to act via an eIF 4E and eIF 2 alpha mediated pathway . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
However , in islets , no change in eIF 2 alpha phosphorylation was seen under conditions where eIF 2B activity was increased , implying that glucose regulates eIF 2B via an alternative pathway . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The DnaJ sequences , present at the carboxyl terminus of P 58 , were dispensable for binding in vitro , while sequences containing the eIF 2 alpha similarity region were essential for efficient complex formation . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
Regulation of gene expression for translation initiation factor eIF 2 alpha : importance of the 3 ' untranslated region . ^^^ Gene expression of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) , involves transcriptional and post transcriptional mechanisms . eIF 2 alpha is a single copy gene expressing two mRNAs , 1 . 6 and 4 . 2 kb in size . ^^^ Four polyadenylation sites were identified within the 3 ' untranslated region ( UTR ) of eIF 2 alpha , only two of which are normally utilized in human and mouse tissues . ^^^ Polyadenylation site selection and mRNA stability differ for the two mRNAs of eIF 2 alpha . ^^^ These activities might be modulated by sequence elements contained within the untranslated regions of the eIF 2 alpha gene . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
A eukaryotic translation initiation factor 2 ( eIF 2 ) associated 67 kDa glycoprotein ( p 67 ) protects the eIF 2 alpha subunit from inhibitory phosphorylation by eIF 2 kinases , and this promotes protein synthesis in the presence of active eIF 2 alpha kinases in vitro [ Ray , M . ^^^ We now report the following . ( 1 ) Transient transfection of COS 1 cells with a p 67 expression vector increased p 67 synthesis by 20 fold over endogenous levels in the isolated subpopulation of transfected cells . ( 2 ) Cotransfection of p 67 cDNA increased translation of plasmid derived mRNAs . ( 3 ) Overexpression of p 67 reduced phosphorylation of coexpressed eIF 2 alpha . ( 4 ) p 67 synthesis was inhibited by cotransfection with an eIF 2 alpha mutant S51D , a mutant that mimics phosphorylated eIF 2 alpha , indicating that p 67 can not bypass translational inhibition mediated by phosphorylation of the eIF 2 alpha subunit . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Although phosphorylation of eIF 2 alpha has been shown to inhibit global protein synthesis , amino acid starvation results in a specific activation effect on GCN 4 mRNA translation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
When neurons cultured in serum free medium are exposed to complete medium for only 24 h , there is a clear decrease in the phosphorylation of eIF 2 alpha ( 16 3 % ) . ^^^ These changes in phosphorylation of eIF 2 alpha in normal mammalian cells in response to changes in the extracellular medium are reported here for the first time . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Our results show , in primary neuronal cultures , that the treatment with the Ca2+ ionophore A 23187 induces an increase in the phosphorylation of the alpha subunit of eIF 2 ( eIF 2 alpha ) and inhibition of protein synthesis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This report shows that ( 1 ) the carboxyl terminus of MyD 116 interacts with protein phosphatase 1alpha in yeast , and both MyD 116 and gamma ( 1 ) 34 . 5 interact with protein phosphatase 1alpha in vitro ; ( 2 ) protein synthesis in infected cells is strongly inhibited by okadaic acid , a phosphatase 1 inhibitor ; and ( 3 ) the alpha subunit in purified eIF 2 phosphorylated in vitro is specifically dephosphorylated by S 10 fractions of wild type infected cells at a rate 3000 times that of mock infected cells , whereas the eIF 2alpha P phosphatase activity of gamma ( 1 ) 34 . 5 virus infected cells is lower than that of mock infected cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Use of vertical slab isoelectric focusing and immunoblotting to evaluate steady state phosphorylation of eIF 2 alpha in cultured cells . ^^^ However , the method is more difficult to apply to the analysis of eIF 2 alpha phosphorylation in cultured cells . ^^^ In part this reflects the fact that the protein content of cultured cell extracts is rarely as high as that found in extracts produced from reticulocytes , and in part this reflects the fact that some component ( s ) of cell extracts interferes with the entry of eIF 2 alpha into the isoelectric focusing gel . ^^^ 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: P20042 and P05198	Pubmed	SVM Score :0.0
The increased eIF 2alpha phosphorylation that occurs at high concentrations of PQQ inhibits eIF 2B activity , presumably due to formation of a 15S complex [ eIF 2 ( alphaP ) . eIF 2B ] in which eIF 2B becomes non functional . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
PKI specifically inhibits the phosphorylation of the plant encoded eIF 2 alpha kinase ( pPKR ) as well as plant and human eIF 2 alpha phosphorylation . ^^^ Phosphorylation of eIF 2 alpha is a classical mechanism for the downregulation of protein synthesis suggesting that inhibition of pPKR activity by PKI may contribute to the dramatic and rapid increase in protein synthesis observed during seed germination . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The role of chaperones in regulating eIF 2 alpha kinase activities , eIF 2 cycling , and ribosomal loading on mRNA is emphasized . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
Because the overall translation initiation rate is typically regulated by altering the phosphorylation of serine 51 on the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha ) , we used an antibody specific to phosphorylated eIF 2 alpha [ eIF 2 ( alpha P ) ] to study the regional and cellular distribution of eIF 2 ( alpha P ) in normal , ischemic , and reperfused rat brains . ^^^ Western blots of brain postmitochondrial supernatants revealed that approximately 1 % of all eIF 2 alpha is phosphorylated in controls , eIF 2 ( alpha P ) is not reduced by up to 30 minutes of ischemia , and eIF 2 ( alpha P ) is increased approximately 20 fold after 10 and 90 minutes of reperfusion . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The intraischemic and early reperfusion changes of protein synthesis in the rat brain . eIF 2 alpha kinase activity and role of initiation factors eIF 2 alpha and eIF 4E . ^^^ Eukaryotic initiation factor 2 ( eIF 2 ) presented almost basal activity and levels after 30 minute normothermic ischemia , and the amount of phosphorylated eIF 2 alpha in these samples , as well as in sham control samples , was undetectable . ^^^ After reperfusion , eIF 4E phosphorylation was almost completely restored to basal levels ( 29 % ) , whereas the level of phosphorylated eIF 2 alpha was higher ( 13 % ) than in controls and ischemic samples ( both less than 2 % ) . eIF 2 alpha kinase activity in vitro as measured by phosphorylation of endogenous eIF 2 in the presence of ATP / Mg2+ , was higher in ischemic samples ( 8 % ) than in controls ( 4 % ) . ^^^ The levels of the double stranded activated eIF 2 alpha kinase were slightly higher in ischemic animals than in controls . ^^^ On the contrary , phosphorylation of eIF 2 alpha , by an eIF 2 alpha kinase already activated during ischemia , represents a plausible mechanism for explaining the inhibition of translation during reperfusion . . ^^^
Interacting proteins: P20042 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 . ^^^ Furthermore , forced expression of a nonphosphorylatable S51A mutant eIF 2 alpha partially protected cells from TNF alpha induced apoptosis , and expression of a S51D mutant eIF 2 alpha , a mutant that mimics phosphorylated eIF 2 alpha , was sufficient to induce apoptosis . ^^^ Taken together , these studies identify a novel requirement for PKR in stress induced apoptosis that is mediated through eIF 2 alpha phosphorylation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Changes in the expression of the heme regulated eIF 2 alpha kinase and heat shock proteins in rabbit reticulocytes maturing during recovery from anemia . ^^^ Changes in the expression of the heme regulated eIF 2 alpha kinase ( HRI ) , heat shock proteins ( Hsps , Hsp 90 , and 70 ) and their associated cohorts ( p 60 and p 23 ) were studied in maturing rabbit reticulocytes during recovery from anemia . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Inhibition of protein synthesis by nitric oxide correlates with cytostatic activity : nitric oxide induces phosphorylation of initiation factor eIF 2 alpha . ^^^ Phosphorylation of eIF 2 alpha was examined as a possible mechanism for the suppressed protein synthesis by NO . ^^^ Mechanistic studies revealed that iNOS expression in RAW264 . 7 cells resulted in the phosphorylation of eIF 2 alpha and inhibition of the 80S ribosomal complex formation . ^^^ CONCLUSIONS : These results suggest that NO suppresses protein synthesis by stimulating the phosphorylation of eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We examined the isoforms of eIF4B and the alpha and beta subunits of eIF 2 during the development and germination of wheat seed to determine whether the differences in their phosphorylation state are because of tissue specific regulation or occur concomitant with changes in protein synthetic activity during development . eIF2alpha underwent phosphorylation through several intermediate isoforms that correlated with the increase and subsequent reduction in protein synthetic activity characteristic of seed development . eIF2beta and eIF4B , present as highly phosphorylated isoforms during early seed development , underwent dephosphorylation during late development . eIF4B was rapidly phosphorylated within 20 h of germination , whereas eIF2alpha did not undergo dephosphorylation until 48 60 h of growth . ^^^
Interacting proteins: P20042 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 ) . ^^^ The time of induced glycosyl modification at the later stages of the heat shock correlates with the reduced level of eIF 2 alpha phosphorylation . ^^^
Interacting proteins: P20042 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: P20042 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 . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
Inhibition occurs at the level of polypeptide chain initiation and is accompanied by the phosphorylation of the alpha subunit of initiation factor eIF 2 and the caspase dependent cleavage of initiation factors eIF4G , eIF4B , eIF2alpha and the p 35 subunit of eIF 3 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Hsp 90 regulates p 50 ( cdc 37 ) function during the biogenesis of the activeconformation of the heme regulated eIF 2 alpha kinase . ^^^ In this report , we examined whether p 50 ( cdc 37 ) is required for the biogenesis of the heme regulated eIF 2 alpha kinase ( HRI ) in reticulocyte lysate . p 50 ( cdc 37 ) interacted with nascent HRI co translationally and this interaction persisted during the maturation and activation of HRI . p 50 ( cdc 37 ) stimulated HRI ' s activation in response to heme deficiency , but did not activate HRI per se . p 50 ( cdc 37 ) function was specific to immature and inactive forms of the kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Together these results indicate that an eIF2alpha phosphatase , probably protein phosphatase 1 , is implicated in the ischemia induced eIF 2 ( alphaP ) accumulation in PC 12 cells . . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
The translation inhibition correlated with an increased phosphorylation of the alpha subunit of eIF 2 ( eIF 2 alpha ) ( 25 % vs . 7 % , for FCCP treated and control cells , respectively ) and a 1 . 7 fold increase in the double stranded RNA dependent protein kinase activity . ^^^ No changes in the PKR endoplasmic reticulum related kinase or eIF 2 alpha phosphatase were found . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Hybridization of RNA samples from either chicken osteoblasts or a human osteoblast cell line with a probe for a subunit of human eukaryotic initiation of translation factor 2 ( eIF2alpha ) , the housekeeping initiation factor , indicates that levels of eIF 2 remain low . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The purified enzyme has dsRNA dependent activation and phosphorylates the translation initiation factor eIF 2 alpha . ^^^ K3L inhibited both autophosphorylation of PKR and phosphorylation of eIF 2 alpha , whereas VAI RNA inhibited only autophosphorylation . ^^^
Interacting proteins: P20042 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 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The rate of protein synthesis in mammals is largely regulated by phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 ) that is modulated by the cellular glycoprotein , p 67 , due to its protection of eIF2alpha phosphorylation ( POEP ) activity . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We now describe the identification of S . mansoni eukaryotic translation initiation factor 2 alpha subunit ( eIF 2 alpha ) , through its interaction with SmRK 1 in a yeast two hybrid assay . ^^^ S . mansoni eIF 2 alpha also interacts with human TGF beta receptors . ^^^ Both T beta RI and T beta RII phosphorylate eIF 2 alpha in vitro , at sites other than the previously described eIF 2 alpha phosphorylation sites . ^^^ EIF 2 alpha also modulates signaling by TGF beta receptors ; however , in contrast to 14 3 3 epsilon , eIF 2 alpha overexpression inhibits the TGF beta driven response . ^^^ These data suggest a novel function for eIF 2 alpha in the TGF beta signaling pathway . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This diminished activity was not caused by a reduction in the content of eIF 2B epsilon or the content and phosphorylation state of eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Environmental stress induced phosphorylation of eIF2alpha inhibits protein translation by reducing the availability of eIF 2 GTP tRNA ( 1 ) Met , the ternary complex that joins initiator tRNA ( Met ) to the 43S preinitiation complex . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the alpha subunit of eIF 2 [ eIF 2 ( alphaP ) ] by the endoplasmic reticulum transmembrane eIF2alpha kinase PERK occurs immediately on reperfusion and inhibits translation initiation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Peptide Phi , but not peptide K , blocked Hsp90 / Hsc70 dependent transformation of the heme regulated eIF 2 alpha kinase ( HRI ) into an active , heme regulatable kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
It is also observed here that heat treatment stimulates the phosphorylation of rabbit reticulocyte eIF 2 alpha but not the alpha subunit ( p 41 42 doublet ) of WG eIF 2 . ^^^ A phosphospecific anti eIF 2 alpha antibody recognizes the WG eIF 2 alpha ( P ) that is phosphorylated by an authentic eIF 2 alpha kinase such as double stranded RNA dependent protein kinase , but it is unable to recognize the eIF 2 alpha that is phosphorylated in NEM treated lysates . ^^^ These findings therefore suggest that phosphorylation of WG eIF 2 alpha in NEM treated lysates occurs on a site different from the serine 51 residue that is phosphorylated by authentic eIF 2 alpha kinases . ^^^ In addition , it also suggests that WG eIF 2 alpha , unlike reticulocyte eIF 2 alpha , is phosphorylated by eIF 2 alpha kinases and also by other kinases . ^^^ Consistent with this idea , it has been observed here that casein kinase 2 ( CKII ) phosphorylates WG eIF 2 alpha and the phosphorylation is enhanced by NEM in vitro and in lysates . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This inhibition is associated with the increased phosphorylation of eukaryotic initiation factor ( eIF 2 ) alpha , increased association of eIF4E with the inhibitory eIF4E binding protein ( 4E BP 1 ) , and specific cleavages of eIF4B and eIF2alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The reduction in protein synthesis rate correlates with increased phosphorylation of the translation initiation factor eIF 2 alpha . ^^^ 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 . ^^^ These data demonstrate a connection between eIF 2 alpha phosphorylation and activation of cellular IRES elements . ^^^ It suggests that phosphorylation of eIF 2 alpha , known to be important for cap dependent translational control , serves to fine tune the translation efficiency of different mRNA subsets during the course of differentiation and has the potential to regulate expression of IRES containing mRNAs under a range of physiological circumstances . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This is accomplished by recruiting protein phosphatase 1 to dephosphorylate the alpha subunit of translation initiation factor eIF 2 ( eIF 2 alpha ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We show that , in a natural infection of MDBK cells , cpBVDV activates the ER transmembrane kinase PERK ( PKR like ER kinase ) and causes hyperphosphorylation of the translation initiation factor eIF 2 alpha , consistent with the induction of an ER stress response . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of eIF2alpha by one or more of these kinases reduces the concentration of eIF 2 guanosine triphosphate ( GTP ) transfer ribonucleic acid for methionine ( tRNA ( Met ) ) , the ternary complex that loads tRNA ( Met ) onto the small ribosomal subunit to initiate protein translation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Molecular cloning and sequencing of the human heme regulated eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) kinase from bone marrow culture . ^^^ The cDNA encoding human heme regulated eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) kinase was cloned from a human bone marrow culture . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The growth arrest and DNA damage inducible protein , GADD 34 , associates with protein phosphatase 1 ( PP 1 ) and promotes in vitro dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 , ( eIF 2 alpha ) . ^^^ In this report , we show that the expression of human GADD 34 in cultured cells reversed eIF 2 alpha phosphorylation induced by thapsigargin and tunicamycin , agents that promote protein unfolding in the endoplasmic reticulum ( ER ) . ^^^ GADD 34 expression also reversed eIF 2 alpha phosphorylation induced by okadaic acid but not that induced by another phosphatase inhibitor , calyculin A ( CA ) , which is a result consistent with PP 1 being a component of the GADD 34 assembled eIF 2 alpha phosphatase . ^^^ N terminal deletions of GADD 34 established that while PP 1 binding was necessary , it was not sufficient to promote eIF 2 alpha dephosphorylation in cells . ^^^ These data provide new insights into the mode of action of GADD 34 in assembling an ER associated eIF 2 alpha phosphatase that regulates protein translation in mammalian cells . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
To control this process we constructed a nonphosphorylatable Ser ( 51 ) Ala site directed mutant of eIF2alpha , a subunit of the trimeric eIF 2 complex that is implicated in regulation of the global rate of mRNA translation initiation in eukaryotic cells . ^^^ Phosphorylation of eIF2alpha by protein kinases inhibits eIF 2 activity and is known to increase as cells perceive a range of stress conditions . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor 2 ( eIF 2 ) associated glycoprotein , p 67 , has protection of eIF2alpha phosphorylation ( POEP ) activity , and this activity requires lysine rich domains 1 and 2 of p 67 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Both toxins increased the phosphorylation of UPR proteins , PERK and eIF 2 alpha , but only 6 OHDA increased phosphorylation of c Jun . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Additional studies suggested that p 58 ( IPK ) induction was mediated via ATF 6 and that P 58 ( IPK ) played a role in down regulating the activity of the pancreatic eIF 2 kinase / eukaryotic initiation factor 2alpha ( eIF2alpha ) like ER kinase / activation transcription factor ( ATF ) 4 pathway . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
After stimulation by cytokines , uptake of L arginine negatively regulates the phosphorylation status of the eukaryotic initiation factor ( eIF 2 alpha ) , which , in turn , regulates translation of iNOS mRNA . eIF 2 alpha phosphorylation correlates with phosphorylation of the mammalian homolog of yeast GCN 2 eIF2 alpha kinase . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In vivo replication of an ICP34 . 5 second site suppressor mutant following corneal infection correlates with in vitro regulation of eIF 2 alpha phosphorylation . ^^^ We show here that the inability of ICP34 . 5 mutants to grow in vitro is due specifically to the accumulation of phosphorylated eIF 2 alpha . ^^^ The phosphorylation state of eIF 2 alpha following in vitro infection with the suppressor virus was examined to determine if in vivo differences could be attributed to differential regulation of eIF 2 alpha phosphorylation . ^^^ The suppressor virus prevented accumulation of phosphorylated eIF 2 alpha , while the wild type virus substantially reduced eIF 2 alpha phosphorylation levels . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This requires the carboxyl terminus of the gamma ( 1 ) 34 . 5 protein to recruit PP 1 , forming a high molecular weight complex that dephosphorylates the alpha subunit of translation initiation factor eIF 2 ( eIF 2alpha ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Rapamycin induced translational derepression of GCN 4 mRNA involves a novel mechanism for activation of the eIF 2 alpha kinase GCN 2 . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
IfkA , a presumptive eIF 2 alpha kinase of Dictyostelium , is required for proper timing of aggregation and regulation of mound size . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
It was found that this cDNA was highly homologous to Schistosoma mansoni eukaryotic translation initiation factor 2 alpha subunit ( eIF 2 alpha ) mRNA . ^^^ According to the known EST sequence , the 3 ' terminal primer that matched the sequencing primer for the 5 ' terminal in pTriplEx 2 plasmid was designed and used to amplify the full length open reading frame ( ORF ) sequence of the eIF 2 alpha from the cDNA Library . ^^^ RESULT : A novel cDNA sequence coding for a eIF 2 alpha was found from the cDNA library of Schistosoma japonicum cercariae , which was highly homologous to the known Schistosoma mansoni eIF 2 alpha mRNA , with the homology of 87 % at the nucleotide level and 79 % at the amino acid level . ^^^ CONCLUSION : The novel gene found by EST strategy may encode a eIF 2 alpha which is highly homologous to Schistosoma mansoni eukaryotic eIF 2 alpha mRNA . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor 2 ( eIF 2 ) associated glycoprotein p 67 blocks eIF2alpha phosphorylation by kinases , and its N terminal 1 97 amino acid segment can induce efficient translation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
TGF alpha stimulated the phosphorylation of the eukaryotic initiation factor 4E ( eIF4E ) but did not affect eIF 2 alpha , two proteins involved in translation regulation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
GADD 34 was recently identified as the factor that activates the type 1 protein serine / threonine phosphatase ( PP 1 ) , which dephosphorylates eIF 2 alpha during cellular stresses . ^^^ Our study delineates a negative feedback regulatory loop in which the eIF 2 alpha controlled inhibition of protein translation leads to GADD 34 induction , which promotes translational recovery . ^^^ We show that activating transcription factor 4 ( ATF 4 ) , which is paradoxically translated during the eIF 2 alpha mediated translational block , is required for the transactivation of the GADD 34 promoter in response to ER stress and amino acid deprivation . ^^^ Examination of ATF 4 / MEFs revealed an absence of GADD 34 induction , prolonged eIF 2 alpha phosphorylation , delayed protein synthesis recovery , and diminished translational up regulation of BiP during ER stress . ^^^ These studies demonstrate the essential role of GADD 34 in the resumption of protein synthesis , define the pathway for its induction , and reveal that cytoprotective unfolded protein response targets like BiP are sensitive to the eIF 2 alpha mediated block in translation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Potential regulation of eIF 2 alpha phosphorylation in differentiated PC 12 cells . ^^^ H ( 2 ) O ( 2 ) treatment increased eIF 2 alpha phosphorylated levels ( eIF 2 alpha P ) in a time and dose dependent fashion and promoted protein synthesis inhibition . ^^^ Interestingly , NAC pretreatment protected cells from H ( 2 ) O ( 2 ) induced PP 1 inactivation and , consequently , it abolished increased H ( 2 ) O ( 2 ) induced eIF 2 alpha phosphorylation and protein synthesis inhibition . ^^^ In addition , PP 1 inhibitor tautomycin prevented both NAC induced PP 1 reactivation and eIF 2 alpha P dephosphorylation in H ( 2 ) O ( 2 ) treated cells . ^^^ Taken together , our findings support a role for PP 1 in eIF 2 alpha phosphorylation and oxidative stress triggered translation down regulation . . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylated forms of eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) and RNA dependent protein kinase like ER eIF 2 alpha kinase ( PERK ) , both of which play active roles in apoptosis , were increased in hippocampal CA 1 neurons after ischemia but to a lesser degree in the transgenic animals . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Sequences from subtypes 1b and 4c / d resembled more closely the phosphorylation sites of protein kinase R and eIF 2 alpha than sequences from genotypes 2c and 3a , the latter with higher response rates to interferon alpha ( IFN alpha ) treatment . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
High physiological levels of LMP 1 result in phosphorylation of eIF 2 alpha in Epstein Barr virus infected cells . ^^^ We also found that induction of expression of LMP 1 or of a derivative of LMP 1 with its transmembrane domain fused to green fluorescent protein instead of its carboxy terminal signaling domain resulted in phosphorylation of eIF 2 alpha in EBV negative Burkitt ' s lymphoma cells . ^^^ This induction of phosphorylation of eIF 2 alpha was also detected in EBV infected lymphoblasts , in which high levels of LMP 1 correlated with high levels of phosphorylation of eIF 2 alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Nevertheless , eIF2B mediated guanine nucleotide exchange activity downstream of eIF 2 was frequently aberrant in transformed cells , neutralizing eIF2alpha phosphorylation and permitting VSV mRNA translation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Using codon optimization , chaperone co expression , and rational mutagenesis for production and NMR assignments of human eIF 2 alpha . ^^^ This approach was developed as we tried to produce a NMR suitable sample of the 35 kDa human translation initiation factor eIF 2 alpha , a protein that expresses poorly in E . coli and has very low solubility . ^^^ Combining all these methods made it possible to produce from a one liter preparation a 0 . 5 mM sample of human eIF 2 alpha that showed well resolved NMR spectra and enabled nearly complete assignment of the protein . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In addition to characterizing Toxoplasma eIF2alpha ( TgIF2alpha ) , we have discovered a novel eIF 2 protein kinase , designated TgIF2K A ( Toxoplasma gondii initiation factor 2kinase ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Control of alpha subunit of eukaryotic translation initiation factor 2 ( eIF 2 alpha ) phosphorylation by the human papillomavirus type 18 E 6 oncoprotein : implications for eIF 2 alpha dependent gene expression and cell death . ^^^
Interacting proteins: P20042 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: P20042 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 . ^^^ Phospho eIF 2 alpha immunoreactivity was detected in some oligodendrocytes in hindbrain sections of control animals . ^^^ Alternatively , phospho PKR and phospho eIF 2 alpha may promote apoptosis as a way to regulate T cell number in the CNS . ^^^ The expression of phospho eIF 2 alpha in oligodendrocytes during EAE likely is involved with inhibition of protein translation , which is a protective mechanism used to promote cell survival in response to inflammation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In ts 1 infected C 1 cells , an unfolded protein response was identified by activation of the ER resident transmembrane protein kinase PERK , an event that leads to hyperphosphorylation of eIF 2 alpha , up regulation of GRP 78 , increased amounts of GADD153 / CHOP , and cleavage of procaspase 12 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The structural and functional similarities found between eIF2alpha / eIF2gamma and eEF1Balpha / eEF1A suggest a model for the interaction of eIF2alpha with eIF2gamma , and eIF 2 with Met tRNAiMet . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Met tRNAi ) and the dephosphorylation of eIF 2 alpha . ^^^ However , we show that glucose stimulates the dephosphorylation of eIF 2 alpha in MIN 6 cells and the assembly of the translational ternary complex , eIF 2 GTP . ^^^ The changes in the phosphorylation of eIF 2 alpha are not mediated by the PKR like endoplasmic reticulum eIF 2 alpha kinase ( PERK ) , because PERK is not phosphorylated at low glucose concentrations and overexpression of a dominant negative form of PERK has no significant effect on either glucose stimulated protein synthesis or the phosphorylation of eIF 2 alpha . ^^^ Taken together , these results indicate that glucose stimulated protein synthesis in pancreatic beta cells is regulated by a mechanism largely independent of the activity of mammalian target of rapamycin , but which is likely to be dependent on the availability of the translational ternary complex , regulated by the phosphorylation status of eIF 2 alpha . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The cowpox virus host range gene , CP 77 , affects phosphorylation of eIF 2 alpha and vaccinia viral translation in apoptotic HeLa cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
In contrast , PEG 3 was unable to block other GADD 34 induced changes , including eIF 2 alpha dephosphorylation , indicating that its effects on GADD 34 may be related more to its effect on cell growth rather than a global inhibitor of all GADD 34 functions . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This analysis of eIF2alpha phosphorylation , coupled with earlier findings that the eIF4F complex is modified earlier during VSV infection , supports a temporal / kinetic model of translation control , where at times soon after infection , changes in the eIF4F complex result in the inhibition of host protein synthesis ; at later times , inactivation of the eIF 2 complex blocks VSV protein synthesis . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor 2A ( eIF2A ) has been shown to direct binding of the initiator methionyl tRNA ( Met tRNA ( 1 ) ) to 40 S ribosomal subunits in a codon dependent manner , in contrast to eIF 2 , which requires GTP but not the AUG codon to bind initiator tRNA to 40 S subunits . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Concurrently , a marked ( > 80 % ) suppression of de novo hepatocellular protein synthesis was also observed , along with a significantly enhanced phosphorylation of the alpha subunit of the eukaryotic initiation factor eIF 2 ( eIF2alpha ) , as monitored by the phosphorylated eIF2alpha / total eIF2alpha ratio in these heme depleted cells . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Renal ischemia and reperfusion activates the eIF 2 alpha kinase PERK . ^^^ Several pathways have been identified whereby cell stress inhibits translation initiation via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 alpha , phospho form eIF 2 alpha ( P ) ] . ^^^ Here , we report a 20 fold increase in eIF 2 alpha ( P ) in kidney homogenates following 10 min of cardiac arrest induced ischemia and 10 min reperfusion . ^^^ Using immunohistochemistry , we observed eIF 2 alpha ( P ) in tubular epithelial cells in both cortex and medulla , where the greatest eIF 2 alpha ( P ) staining was found in epithelial cells of the so called watershed area at the corticomedullary junction . ^^^ We further show that increased eIF 2 alpha ( P ) is accompanied by activation of the PKR like endoplasmic reticulum eIF 2 alpha kinase ( PERK ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Markers of endoplasmic reticulum ( ER ) stress , specifically the CCAAT / enhancer binding protein ( CHOP ) , the glucose related protein 78 ( GRP 78 ) , and phosphorylated eukaryotic initiation factor 2 alpha ( eIF 2 alpha ) , were also up regulated in ts 1 infected C 1 astrocytes . ^^^
Interacting proteins: P20042 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: P20042 and P05198	Pubmed	SVM Score :0.0
Mice devoid of the eIF 2 kinase GCN 2 [ general control non derepressible 2 or EIF2AK4 ( eIF2alpha kinase 4 ) ] show sensitivity to nutritional deficiencies and aberrant eating behaviours , and deletion of PEK [ pancreatic eIF2alpha kinase or PERK ( RNA dependent protein kinase like endoplasmic reticulum kinase ) or EIF2AK3 ] leads to neonatal insulin dependent diabetes , epiphyseal dysplasia and hepatic and renal complications . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This modification of eIF 2 does not restrict viral replication ; SV 26S mRNA initiates translation with canonical methionine in the presence of high levels of phosphorylated eIF2alpha . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Results of UV cross linking experiments and of assays of 48S complex formation done using alpha subunit deficient eIF 2 indicate that eIF2alpha ' s interaction with the ( ) 3 purine is responsible for recognition of the ( ) 3 context position by 43S complexes and suggest that the ( + ) 4 purine / AA ( 1818 1819 ) interaction might be responsible for recognizing the ( + ) 4 position . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor 2 ( eIF 2 ) associated glycoprotein , p 67 , plays an important role in protecting eIF2alpha from phosphorylation by eIF2alpha specific kinases . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of eIF 2alpha is almost completely inhibited by 20 35 muM hemin , whereas phosphorylation of eIF 2beta is only partially inhibited . ^^^ The protein kinase activity that modifies eIF 2alpha has been shown to have inhibitory activity in the cell free protein synthesizing system , whereas the protein kinase for eIF 2beta has no effect . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The inhibition of eIF 2B activity was associated with a 2 . 4 fold increase in the proportion of the alpha subunit of eIF 2 in the phosphorylated form . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
GDP can participate in an eIF 2B catalyzed GDP / GTP exchange reaction to reform the Met tRNA ( f ) . eIF 2 . ^^^ In contrast , when 60 S ribosomal subunits were preincubated with either free eIF 2 or with eIF 2 . eIF 2B complex and then added to a reaction containing both the 40 S initiation complex and eIF 5 , the eIF 2 . ^^^ Under similar experimental conditions , preincubation of 60 S ribosomal subunits with purified eIF 2B ( free of eIF 2 ) failed to cause release of eIF 2 . ^^^ GDP does not act as a direct substrate for eIF 2B mediated release of eIF 2 from ribosomes . ^^^ Rather , the affinity of 60 S ribosomal subunits for either eIF 2 , or the eIF 2 moiety of the eIF 2 . eIF 2B complex , prevents association of 60 S ribosomal subunits with eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Close values of dissociation constants for WGeIF 2 complexes with guanine nucleotides suggest that at a sufficiently high [ GTP ] / [ GDP ] ratio the nucleotide exchange in wheat cells may take place without the participation of specific factor ( eIF 2B ) which catalyzes the nucleotide exchange on eIF 2 from mammalian cells . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
One of the factors involved in the postfertilization activation of protein synthesis in the sea urchin , Strongylocentrotus purpuratus , is the activation of eIF 2B , the initiation factor responsible for guanine nucleotide exchange on eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have found that purified eIF 2B dissociates eIF 2 . [ 3H ] GDP as efficiently in the presence of GTP as it does in the presence of GDP provided Met tRNA ( fMet ) is added . tRNA ( fMet ) is ineffective , and there is no Met tRNA ( fMet ) requirement for exchange with GDP . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The influence of changing concentrations of GDP , methionyl tRNAi , eIF 2 and eIF 2B on possible rates of initiation of protein synthesis have been explored in calculations based on previously derived rate constants for interaction of the components involved in formation of ternary or quaternary complexes of eIF 2B , eIF 2 , GTP and Met tRNAi . ^^^ Biochem . 175 , 93 : 1988 ) of higher concentrations of eIF 2 and eIF 2B in cells than hitherto proposed become necessary to support known rates of initiation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Int . 22 , 523 533 : 1990 ) for the reactions catalysed by eIF 2B ( GEF ) in which free GDP exchanges with GDP bound to eIF 2 have been re evaluated using the computational procedures developed by Chau et al . ( J . ^^^ GDP ( eIF 2B . eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
GDP ) to act as a competitive inhibitor of eIF 2B catalysed exchange of eIF 2 bound GDP has been investigated by modelling data provided by Rowlands et al . ( J . ^^^ GDP without substantial increase in its affinity for eIF 2B over that of eIF 2 . ^^^ Classic double reciprocal plots for competitive inhibition were found only when [ eIF 2B ] was low in relation to [ eIF 2 ( alpha P ) . ^^^ Relatively high cellular [ eIF 2B ] lessens the inhibitory effect of eIF 2 ( alpha P ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Stimulation of translation correlates with enhanced phosphorylation of eIF 4F , eIF 4B , eIF 2B , eIF 3 and ribosomal protein S 6 , whereas inhibition correlates with phosphorylation of eEF 2 and the alpha subunit of eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Published data have been analysed to determine the rate constants governing the exchange of GDP in the complex of the eukaryotic protein synthesis initiation factor eIF 2 with GDP , catalysed by eIF 2B . ^^^ The interaction of eIF 2B with eIF 2 . ^^^ Assuming a substituted enzyme mechanism that leads to displacement of GDP and ultimately to formation of a quaternary complex eIF 2B . eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The former is likely a result of the latter , since we find that reticulocyte lysate has about twice the eIF 2B necessary to recycle the eIF 2 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Met tRNAf ] as well as in the eIF 2 . eIF 2B complex the alpha subunit of eIF 2 was found to be specifically labeled . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Kinetic constants in the functioning of eIF 2 and eIF 2B . ^^^ Minimum rate constants for reactions catalysed by the eukaryotic initiation factor eIF 2B in promoting formation of the ternary complex eIF 2 . ^^^ The most plausible sequence of reactions in vivo is when eIF 2B remains bound to eIF 2 . ^^^ Rate constants for reaction of eIF 2B and eIF 2 . ^^^ This finding suggests some form of sequestration of eIF 2 and eIF 2B in the cell to facilitate interaction , which may result in only a portion of cellular eIF 2 being actively engaged in initiation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Available data for the formation of the ternary complex eIF 2 10 GTP 10 methionyl tRNAi involved in eukaryotic initiation and of the inhibition of ternary complex formation by GDP have been examined with a view to determining the mechanism by which eIF 2B facilitates nucleotide exchange . ^^^ Two mechanisms have been considered first a displacement reaction in which eIF 2B displaces GDP and GTP in a manner analogous to a `` ping pong ' ' enzyme mechanism , and secondly the possibility that binding of eIF 2B to eIF 2 nucleotide complexes enhances the rate of nucleotide exchange without itself inducing nucleotide displacement . ^^^ Comparison has been made between the properties of eIF 2 and eIF 2B and of the bacterial elongation factors Tu and Ts . ^^^ This phosphorylation appears to change the equilibria in the reaction mechanism such that the transferred entity ( eIF 2 ) becomes firmly bound to the catalyst ( eIF 2B ) . ^^^ Minimum rate constants for the formation of eIF 2 10 eIF 2B from eIF 2 10 GDP and eIF 2 10 GTP and reverse reactions are derived . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Evaluation and significance of kinetic parameters governing function of protein synthesis initiation factors eIF 2 and eIF 2B . ^^^ Published data dealing with the formation of the ternary complex eIF 2 10 GTP 10 met tRNAi involved in eukaryotic initiation have been evaluated to calculate the expected inhibition by GDP and the role of eIF 2B in limiting this inhibition . ^^^ However , derivation of ' on ' and ' off ' rates for the interaction of GTP and GDP with eIF 2 demonstrates that these are too slow in the absence of eIF 2B to support active protein synthesis , particularly if eIF 2 is released from ribosomes as eIF 2 10 GDP . ^^^ Phosphorylation of the alpha subunit of eIF 2 appears to affect only those parameters influenced by eIF 2B . ^^^ Consideration of the kinetic parameters favours the formation of a ternary complex of eIF 2 10 eIF 2B 10 GDP en route to eIF 2 10 GTP as opposed to displacement of GDP from eIF 2 10 GDP by eIF 2B . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
It is free of eIF 2 , but possesses eIF 2B activity . ^^^ Its purification properties suggest that it is distinct from previously characterized initiation factors , including eIF 2 / eIF 2B complex , and its possible relationship to known initiation factors is discussed . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Translation of exogenous mRNAs in micrococcal nuclease treated extracts from Ehrlich ascites tumor cells is greatly stimulated by the addition of crude initiation factors or initiation factors eIF 2B and eIF 2 containing eIF 2B . ^^^ The requirement for exogenous eIF 2B in micrococcal nuclease treated extracts does not result from either loss or enhanced phosphorylation of eIF 2 during incubation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor 2B ( eIF 2B ) is a heteropentameric guanine nucleotide exchange factor involved in the recycling of eIF 2 during the translation initiation phase of protein synthesis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The eIF 2B epsilon monoclonal antibodies and monoclonal antibodies to the alpha subunit of eIF 2 were then used to directly quantitate the amounts of eIF 2B and eIF 2 in rat liver and rat reticulocytes . ^^^ The ratio of eIF 2B to eIF 2 was found to be approx . 0 . 6 and 0 . 3 in liver and reticulocytes , respectively , supporting the proposition that phosphorylation of only part of the total cellular eIF 2 could potentially sequester all of the eIF 2B into an inactive eIF 2 . eIF 2B complex . ^^^ Overall , the studies presented here are the first to show a direct quantitation of eIF 2 and eIF 2B in different tissues . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Because translation of GCN 4 mRNA is so tightly coupled to eIF 2 activity , genetic analysis of this system has provided unexpected insights into the regulation of eIF 2 and its guanine nucleotide exchange factor , eIF 2B . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Is there a need for channelling in the functioning of the protein synthesis initiation factors eIF 2 and eIF 2B . ^^^ Calculations suggest that despite the very high association rate constant found for the interaction of eIF 2 and eIF 2B under in vitro conditions , it is unlikely that rates in vivo can be high enough to permit measured rates of protein synthesis . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
This is associated with increased phosphorylation of the alpha subunit of the initiation factor eIF 2 , which in turn impairs the activity of the guanine nucleotide exchange factor , eIF 2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We identify here the translational initiation complex , eIF 4F , and the guanine nucleotide exchange factor for eIF 2 , eIF 2B , as the rate controlling components of protein synthesis in immature oocytes of the starfish , Pisaster orchraceus . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We have proposed that reducing eIF 2 activity by phosphorylation of its alpha subunit or by a mutation in the eIF 2 recycling factor eIF 2B allows ribosomes which have translated the 5 ' proximal uORF 1 to bypass uORF 2 to uORF 4 and reinitiate at GCN 4 instead . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The eukaryotic protein synthesis initiation factor , eIF 2B , is a multimeric protein of five different subunits termed alpha , beta , gamma , delta and epsilon , which facilitates recycling of a further factor , eIF 2 , and is an important control point in the initiation process . ^^^ Quantitative studies showed substantial variation in the relative concentrations of eIF 2 and eIF 2B between different rabbit tissues . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Previous genetic and biochemical experiments led to the conclusion that GCD 1 , GCD 2 , and GCN 3 are components of the GCD complex , recently shown to be the yeast equivalent of the mammalian guanine nucleotide exchange factor for eIF 2 , known as eIF 2B . ^^^ Biochemical experiments showing that GCD 6 and GCD 7 copurify and coimmunoprecipitate with GCD 1 , GCD 2 , GCN 3 , and subunits of eIF 2 have confirmed that GCD 6 and GCD 7 are subunits of the GCD eIF 2B complex . ^^^ The fact that all five subunits of yeast eIF 2B were first identified as translational regulators of GCN 4 strongly suggests that regulation of guanine nucleotide exchange on eIF 2 is a key control point for translation in yeast cells just as in mammalian cells . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Preparation of a cell free translation system with minimal loss of initiation factor eIF 2 / eIF 2B activity . ^^^ The block resulted from a decrease in eukaryotic initiation factor 2 ( eIF 2 ) or the guanine nucleotide exchange factor ( eIF 2B ) activity , since the addition of eIF 2 or eIF 2B to these latter extracts substantially improved the capacity of the extract to initiate translation of exogenous mRNA . ^^^ We show that the method of cell extract preparation greatly influences the state of eIF 2 / eIF 2B activity in the resulting extract and that extracts in which this activity is maintained can readily initiate translation on exogenous mRNA and reinitiate on endogenous mRNA . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Computer assisted analysis of amino acid sequences using methods for database screening with individual sequences and with multiple alignment blocks reveals a complex multidomain organization of yeast proteins GCD 6 and GCD 1 , and mammalian homolog of GCD 6 subunits of the eukaryotic translation initiation factor eIF 2B involved in GDP / GTP exchange on eIF 2 . ^^^ It is hypothesized that the nucleotidyltransferase related domain is directly involved in the GDP / GTP exchange , whereas the C terminal conserved domain may be involved in the interaction of eIF 2B , eIF 4 gamma , and eIF 5 with eIF 2 . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The exchange reaction mediated by eIF 2B can be regulated by phosphorylation of eIF 2 on its alpha subunit . ^^^ Mutational analysis in Saccharomyces cerevisiae suggested that the smallest subunit ( the alpha ) is dispensable for exchange , but required for the inhibition of eIF 2B by eIF 2 ( alphaP ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of eIF 2alpha impairs the guanine nucleotide exchange activity of eIF 2B and thereby inhibits or shuts off protein synthesis . ^^^ Delayed addition of hemin to shut off lysates inhibits the eIF 2alpha kinase activity of HRI and restores protein synthesis ; under those conditions , the endogenous phosphatase of the lysate dephosphorylates phosphorylated eIF 2alpha and restores eIF 2B activity . ^^^ The recovery of eIF 2B activity is not affected by protein synthesis inhibitors such as cycloheximide , pactamycin and puromycin , which do not affect the eIF 2alpha phosphorylation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The activity of eIF 2B is inhibited indirectly by phosphorylation of the smallest subunit of eIF 2 which sequesters eIF 2B into an inactive eIF 2 ( alpha P ) . eIF 2B complex . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic initiation factor 2B ( eIF 2B ) is a guanine nucleotide exchange protein involved in the recycling of eIF 2 during peptide chain initiation . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the substrate eIF 2 inhibited the GEF activity of the five subunit eIF 2B ; this inhibition required the eIF 2B alpha subunit . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Addition of eukaryotic initiation factor eIF 2 , eIF 2B , cAMP , MgGTP , or dithiothreitol neither prevented nor reversed the inhibition induced by cisplatin , indicating that the mechanism of cisplatin induced translational inhibition is distinct from the inhibition induced by other toxic heavy metal ions ( Hurst , R . , Schatz , J . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Catalysis of guanine nucleotide exchange on eIF 2 by eIF 2B : is it a sequential or substituted enzyme mechanism . ^^^ The mechanism of action of the eukaryotic initiation factor eIF 2B in catalyzing the exchange of guanine nucleotides bound to eIF 2 is uncertain evidence having been adduced for a sequential mechanism and for a substituted enzyme mechanism . ^^^ Suitable rate constants for a sequential mechanism involving the transient formation of the quaternary complex eIF 2 . eIF 2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Phosphorylation of the translation initiation factor eIF 2alpha downregulates protein synthesis by sequestering the guanylate exchange factor eIF 2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Herein , we explore the evolutionary relationships among the components of bacterial initiation factor 2 ( IF 2 ) and eukaryotic IF 2 ( eIF 2 ) / eIF 2B , i . e . , the initiation factors involved in introducing the initiator tRNA into the translation mechanism and performing the first step in the peptide chain elongation cycle . ^^^ All Archaea appear to posses a fully functional eIF 2 molecule , but they lack the associated GTP recycling function , eIF 2B ( a five subunit molecule ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Hsc 70 suppressed eIF 2alpha phosphorylation and maintained the guanine nucleotide exchange activity of eIF 2B in heme deficient RRL and in hemin supplemented RRL exposed to elevated temperatures ( 42 degrees C ) , denatured protein ( reduced carboxymethylated bovine serum albumin , RCM BSA ) , oxidized glutathione or Hg2+ . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
All such mutations in the beta subunit of eIF 2 ( eIF2beta ) mapped to a region containing a putative zinc finger structure of the C 2 C2 type , indicating that these sequences could be involved in RNA recognition . ^^^ We further show that only one run of lysine residues is sufficient for the in vivo function of eIF2beta , probably through charge interaction , since its replacement by arginines did not impair cell viability , whereas substitution for alanines resulted in inviable cells . mRNA binding , but not GTP dependent initiator Met tRNAMet binding , by the eIF 2 complex was determined to be dependent on the presence of the lysine runs of the beta subunit . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Similar to the eIF2alpha promoter , the eIF2beta promoter is TATA less , CAAT less , and GC rich and contains an alpha Pal binding motif . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
The mechanism for the increased protein synthesis and growth appeared to be a transcriptional upregulation of the eIF 2alpha and eIF 2beta genes . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
To address the role of C . elegans PEK in translational control , we expressed this kinase in yeast and found that it inhibits growth by hyperphosphorylation of eIF 2alpha and inhibition of eIF 2B . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
We show that yeast eIF 5 can bridge interaction in vitro between eIF 3 and eIF 2 by binding simultaneously to the amino terminus of eIF 3 subunit NIP 1 and the amino terminal half of eIF2beta , dependent on a conserved bipartite motif in the carboxyl terminus of eIF 5 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Thus the impaired interaction of these two subunits represents a novel type of defect in eIF 2 function , providing in vivo evidence that the strength of interaction between eIF2beta and eIF2gamma defines the correct usage of the AUG codon for translation initiation . . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Eukaryotic translation initiation factor eIF2beta binds to protein kinase CK 2 : effects on CK2alpha activity . eIF 2 ( eukaryotic translation initiation factor 2 ) is a substrate and an interacting partner for CK 2 ( protein kinase CK 2 ) . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
Mutation at Ser 2 and Ser 67 did not affect eIF2beta integrating into the eIF 2 trimer or being able to complex with eIF 5 and CK2alpha . ^^^ The eIF2beta CT form was also incorporated into the eIF 2 trimer but did not bind to eIF 5 . ^^^
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA
Interacting proteins: P20042 and P05198	Pubmed	SVM Score :0.0
NA