| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Assignment of pancreatic eIF 2alpha kinase ( EIF2AK3 ) to human chromosome band 2p12 by radiation hybrid mapping and in situ hybridization . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| During impaired protein folding and assembly in the endoplasmic reticulum ( ER ) , phosphorylation of eIF2alpha by PEK ( Perk or EIF2AK3 ) is essential for induction of NF kappaB transcriptional activity . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| We find that expression of activating transcription factor 3 ( ATF 3 ) , a member of the ATF / CREB subfamily of basic region leucine zipper ( bZIP ) proteins , is induced in response to endoplasmic reticulum ( ER ) stress or amino acid starvation by a mechanism requiring eIF 2 kinases PEK ( Perk or EIF2AK3 ) and GCN 2 ( EIF2AK4 ) , respectively . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Based on genetic studies of two inbred families , we previously identified the gene responsible for this disorder as EIF2AK3 , the pancreatic eukaryotic initiation factor 2alpha ( eIF2alpha ) kinase . ^^^ |
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| Interacting proteins: Q9NZJ5 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 . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| We report the identification and characterization of a cDNA from rat pancreatic islet cells that encodes a new related kinase , which we term pancreatic eIF 2alpha kinase , or PEK . ^^^ In addition to a catalytic domain with sequence and structural features conserved among eIF 2alpha kinases , PEK contains a distinctive amino terminal region 550 residues in length . ^^^ Using recombinant PEK produced in Escherichia coli or Sf 9 insect cells , we demonstrate that PEK is autophosphorylated on both serine and threonine residues and that the recombinant enzyme can specifically phosphorylate eIF 2alpha on serine 51 . ^^^ In the Saccharomyces model system , PEK functionally substituted for the endogenous yeast eIF 2alpha kinase , GCN 2 , by a process requiring the serine 51 phosphorylation site in eIF 2alpha . ^^^ We also identified PEK homologs from both Caenorhabditis elegans and the puffer fish Fugu rubripes , suggesting that this eIF 2alpha kinase plays an important role in translational control from nematodes to mammals . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Characterization of a mutant pancreatic eIF 2alpha kinase , PEK , and co localization with somatostatin in islet delta cells . ^^^ We report the identification and characterization of a related kinase , PEK , which shares common features with other eIF 2alpha kinases including phosphorylation of eIF 2alpha in vitro . ^^^ In contrast to PKR or HRI , which are dependent on autophosphorylation for their kinase activity , a point mutation that replaced the conserved Lys 614 with an alanine completely abolished the eIF 2alpha kinase activity , whereas the mutant PEK was still autophosphorylated when expressed in Sf 9 cells . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Recently , we identified a new family member , pancreatic eIF 2alpha kinase ( PEK ) from rat pancreas . ^^^ In mammalian cells subjected to ER stress , we found that elevated eIF 2alpha phosphorylation was coincident with increased PEK autophosphorylation and eIF 2alpha kinase activity . ^^^ 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 . ^^^ Furthermore , we found that vaccinia virus K3L protein , an inhibitor of the eIF 2alpha kinase PKR involved in an anti viral defence pathway , also reduced PEK activity . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| However , the recent identification of a trans microsomal membrane eIF2alpha kinase , termed PEK or PERK , suggests that this kinase , and not PKR , might be the kinase that is activated by misfolded protein accumulation . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Despite normal activity of the cognate stress inducible eIF2alpha kinases PERK ( also known as PEK ) and GCN 2 , phospho eIF2alpha levels were markedly diminished in GADD 34 overexpressing cells . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Here we report that mutating the gene encoding the ER stress activated eIF2alpha kinase PERK abolishes the phosphorylation of eIF2alpha in response to accumulation of malfolded proteins in the ER resulting in abnormally elevated protein synthesis and higher levels of ER stress . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK expression was associated with increased phosphorylation of the translation elongation initiation factor 2alpha ( eIF2alpha ) , an event previously shown to block cyclin D 1 translation . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| When activated by their cognate upstream stress signals , the mammalian eIF 2 kinases PERK and GCN 2 repress translation of most mRNAs but selectively increase translation of Activating Transcription Factor 4 ( ATF 4 ) , resulting in the induction of the downstream gene CHOP ( GADD 153 ) . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| However , in all reperfused groups , the RNA dependent protein kinase ( PKR ) like endoplasmic reticulum eIF2alpha kinase ( PERK ) exhibited an isoform mobility shift on SDS PAGE , consistent with the activation of the kinase . ^^^ These data indicate that neither HRI nor GCN 2 are required for the large increase in post ischemic brain eIF2alpha ( P ) , and in conjunction with our previous report that eIF2alpha ( P ) is produced in the brain of reperfused PKR / mice , provides evidence that PERK is the kinase responsible for eIF2alpha phosphorylation in the early post ischemic brain . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Phosphorylation of eukaryotic initiation factor 2 ( eIF 2 ) by pancreatic eIF 2 kinase ( PEK ) , induces a program of translational expression in response to accumulation of malfolded protein in the endoplasmic reticulum ( ER ) . ^^^ We describe the characterization of two regions in the ER luminal portion of the transmembrane PEK that carry out distinct functions in the regulation of this eIF 2 kinase . ^^^ The first region mediates oligomerization between PEK polypeptides , and deletion of this portion of PEK blocked induction of eIF 2 kinase activity . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Endoplasmic reticulum ( ER ) stress is not effectively induced in MEF cells subjected to proteasome inhibition , with minimal activation of the ER stress sensory proteins , eIF2alpha kinase PEK ( PERK / EIF2AK3 ) , IRE 1 protein kinase and the transcription regulator ATF 6 following up to 6 h of proteasome inhibitor treatment . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK has a lumenal domain that is similar to the ER stress sensing lumenal domain of the ER resident kinase Ire 1 , and a cytoplasmic portion that contains a protein kinase domain most similar to that of the known eIF2alpha kinases , PKR and HRI . ^^^ ER stress increases PERK ' s protein kinase activity and PERK phosphorylates eIF2alpha on serine residue 51 , inhibiting translation of messenger RNA into protein . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Three different eIF2alpha kinases have been identified in mammalian cells , the heme regulated inhibitor ( HRI ) , the interferon inducible RNA dependent kinase ( PKR ) and the endoplasmic reticulum resident kinase ( PERK ) . ^^^ |
|
| Interacting proteins: Q9NZJ5 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 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Three stresses were studied that cause the phosphorylation of the translation initiation factor , eIF2alpha , by activating specific kinases : ( 1 ) amino acid starvation , which activates GCN 2 ; ( 2 ) endoplasmic reticulum ( ER ) stress , which activates PKR like ER kinase , PERK kinase ; and ( 3 ) double stranded RNA , which activates double stranded RNA dependent protein kinase ( PKR ) by mimicking viral infection . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Activation of the ER transmembrane eIF2alpha kinase , PERK , induced ATF 4 protein expression , direct binding to the composite site in CHOP promoter , and as a consequence , CHOP protein induction . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK , an ER resident transmembrane protein kinase , is also a sensor for the unfolded protein response ( UPR ) , causing phosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) to inhibit translation initiation . ^^^ Here , we report that the FAD mutant PS 1 disturbs the UPR by attenuating both the activation of PERK and the phosphorylation of eIF2alpha . ^^^ These results suggest that mutant PS 1 impedes general translational attenuation regulated by PERK and eIF2alpha , resulting in an increased load of newly synthesized proteins into the ER and subsequently increasing vulnerability to ER stress . . ^^^ |
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| Interacting proteins: Q9NZJ5 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 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha . ^^^ The endoplasmic reticulum ( ER ) resident eIF2alpha kinase PERK was hyperphosphorylated upon hypoxic stress , and overexpression of wild type PERK increased the levels of hypoxia induced phosphorylation of eIF2alpha . ^^^ Cells stably expressing a dominant negative PERK allele and mouse embryonic fibroblasts with a homozygous deletion of PERK exhibited attenuated phosphorylation of eIF2alpha and reduced inhibition of protein synthesis in response to hypoxia . ^^^ PERK ( / ) mouse embryo fibroblasts failed to phosphorylate eIF2alpha and exhibited lower survival after prolonged exposure to hypoxia than did wild type fibroblasts . ^^^ These results indicate that adaptation of cells to hypoxic stress requires activation of PERK and phosphorylation of eIF2alpha and suggest that the mechanism of hypoxia induced translational attenuation may be linked to ER stress and the unfolded protein response . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| ER function has been shown to be disturbed after transient cerebral ischemia , as indicated by an activation of the ER resident eIF2alpha kinase PERK . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress induced molecular chaperone P58IPK . ^^^ P 58 ( IPK ) interacts with and inhibits the PKR like ER localized eIF2alpha kinase PERK , which is normally activated during the ER stress response to protect cells from ER stress by attenuating protein synthesis and reducing ER client protein load . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Mutations affecting the ER stress activated pancreatic ER kinase ( PERK ) and its downstream effector , the translation initiation complex eukaryotic initiation factor 2 ( eIF 2 ) , have a profound impact on islet cell development , function , and survival . ^^^ PERK mutations are associated with the Wolcott Rallison syndrome of infantile diabetes and mutations that prevent the alpha subunit of eIF 2 from being phosphorylated by PERK , block beta cell development , and impair gluconeogenesis . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Experimental manipulation of IRE 1 , PERK , or eIF2alpha phosphorylation or GRP 78 expression might allow the development of therapeutic strategies for FAD . . ^^^ |
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| Interacting proteins: Q9NZJ5 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 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Functional characterization of Drosophila melanogaster PERK eukaryotic initiation factor 2alpha ( eIF2alpha ) kinase . ^^^ In this study , we have characterized the second eIF2alpha kinase found in Drosophila , a PERK homologue ( DPERK ) . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Perk ( / ) cells , lacking an upstream ER stress activated eIF2alpha kinase that activates Atf 4 , accumulate endogenous peroxides during ER stress , whereas interference with the ER oxidase ERO 1 abrogates such accumulation . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Although ATF 6 was not activated , PERK was maximally activated at 10 minute reperfusion , which correlated with maximal eIF2alpha phosphorylation and protein synthesis inhibition . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Because phosphorylation of eIF2alpha during early brain reperfusion is carried out by PERK , these findings suggest that there is prolonged activation of the unfolded protein response in the reperfused brain . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK and Ire1alpha and eIF2alpha are also activated in calreticulin deficient cells . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK eIF2alpha kinase regulates neonatal growth by controlling the expression of circulating insulin like growth factor 1 derived from the liver . ^^^ Humans afflicted with the Wolcott Rallison syndrome and mice deficient for PERK ( pancreatic endoplasmic reticulum eIF2alpha kinase ) show severe postnatal growth retardation . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Mammalian cells respond to endoplasmic reticulum ( ER ) stress by attenuation of protein translation mediated through the PERK eIF2alpha pathway and transcriptional activation of genes such as Grp78 / BiP encoding ER chaperone proteins . ^^^ The disruption of PERK function or the blocking of eIF2alpha Ser 51 phosphorylation fails to attenuate translation after ER stress and also results in substantial impairment of Grp78 / BiP induction by ER stress . ^^^ We report here that ATF 4 , a transcription factor whose translation is up regulated by the PERK eIF2alpha pathway , can activate the Grp 78 promoter independent of the ERSE . ^^^ Our studies resolve a mechanism responsible for inhibition of Grp 78 mRNA induction by ER stress in cells that are functionally null for PERK or devoid of eIF2alpha phosphorylation . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| The phosphorylation status of eukaryotic initiation factor 2alpha ( eIF2alpha ) and RNA dependent protein kinase like ER eIF2alpha kinase ( PERK ) was investigated in the rat hippocampus after ischemia with and without preconditioning . ^^^ PERK is phosphorylated by ER stress , which phosphorylates eIF2alpha . ^^^ Phosphorylation of eIF2alpha and PERK was confirmed after severe ischemia but was inhibited by preconditioning . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK induces phosphorylation of the eukaryotic initiation factor ( eIF2alpha ) , resulting in a shut down of translation at the initiation step . ^^^ |
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| Interacting proteins: Q9NZJ5 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 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| In these various mouse embryonic fibroblasts , we also provided evidence that Nck modulates the activation of the ER resident eIF2alpha kinase PERK and consequently the phosphorylation of eIF2alpha on Ser 51 in response to stress . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| To study the hypothesized protective role of eIF2alpha phosphorylation in isolation of parallel stress signaling pathways , we fused the kinase domain of pancreatic endoplasmic reticulum kinase ( PERK ) , an ER stress inducible eIF2alpha kinase that is normally activated by dimerization , to a protein module that binds a small dimerizer molecule . ^^^ The activity of this artificial eIF2alpha kinase , Fv2E PERK , is subordinate to the dimerizer and is uncoupled from upstream stress signaling . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Immunoblotting confirmed phosphorylation of the key endoplasmic reticulum stress kinase PERK ( PKR like ER kinase ) and eIF2alpha and induction of their downstream targets such as Bip and GADD 153 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Using wild type mice and copper / zinc superoxide dismutase ( SOD 1 ) transgenic mice , we induced focal cerebral ischemia and compared neuronal degeneration and ER stress , that is , phosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) and RNA dependent protein kinase like ER eIF2alpha kinase ( PERK ) . ^^^ We found that neurons with severe and prolonged phosphorylation of eIF2alpha and PERK underwent later degeneration , and that this was partially prevented by SOD 1 overexpression . ^^^ |
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| Interacting proteins: Q9NZJ5 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 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Hypoxic stress results in a rapid and sustained inhibition of protein synthesis that is at least partially mediated by eukaryotic initiation factor 2alpha ( eIF2alpha ) phosphorylation by the endoplasmic reticulum ( ER ) kinase PERK . ^^^ Changes in mRNA translation during the unfolded protein response are mediated by PERK phosphorylation of the translation initiation factor eIF2alpha at Ser 51 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| It is now known that the PKR like ER kinase ( PERK ) mediated phosphorylation of eukaryotic initiation factor 2alpha ( eIF2alpha ) causes translation inhibition at initial reperfusion . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| UPR activation causes : ( 1 ) a PERK mediated phosphorylation of eIF2alpha , inhibiting protein synthesis to prevent further accumulation of unfolded proteins in the ER and ( 2 ) upregulation of genes coding for ER resident enzymes and chaperones and others , via eIF2alpha ( p ) , and ATF 6 and IRE 1 activation . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| We demonstrate here that another eIF2alpha kinase , the endoplasmic reticulum resident protein kinase PERK , contributes to cellular resistance to VSV infection . ^^^ The higher replication capacity of VSV in PERK ( / ) MEFs results from their inability to attenuate viral protein synthesis due to an impaired eIF2alpha phosphorylation . ^^^ We also show that VSV infected PERK ( / ) MEFs are unable to fully activate PKR , suggesting a cross talk between the two eIF2alpha kinases in virus infected cells . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| We have used a pharmacologically activable version of pancreatic ER kinase ( PERK , an ER stress responsive eIF2alpha kinase ) to uncouple eIF2alpha phosphorylation from stress and found that phosphorylation of eIF2alpha is both necessary and sufficient to activate both NF kappaB DNA binding and an NF kappaB reporter gene . eIF2alpha phosphorylation dependent NF kappaB activation correlated with decreased levels of the inhibitor IkappaBalpha protein . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Increasing intracellular nitric oxide levels by SNAP treatment or inhibiting protein folding in the ER lumen by tunicamycin induced the ER stress response as evidenced by increased protein and gene expression of GADD 153 as well as PERK and eIF 2 alpha phosphorylation , and resulted in apoptosis . ^^^ IL 1beta treatment induced PERK and eIF 2 alpha phosphorylation , but not GADD 153 expression or apoptosis . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Herpes simplex virus 1 infection activates the endoplasmic reticulum resident kinase PERK and mediates eIF 2alpha dephosphorylation by the gamma ( 1 ) 34 . 5 protein . ^^^ Together , these observations suggest that regulation of eIF 2alpha phosphorylation by the gamma ( 1 ) 34 . 5 protein is an efficient way to antagonize the inhibitory activity of PKR as well as PERK during productive infection . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| 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 . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Two major proximal sensors of the UPR are inositol requiring enzyme 1alpha ( IRE1alpha ) , an ER transmembrane protein kinase / endoribonuclease , and ER resident eukaryotic translation initiation factor 2alpha ( eIF2alpha ) kinase ( PERK ) . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| We assessed UPR activation in insulin treated murine peritoneal macrophages using a number of markers including 78 kDa glucose response protein ( GRP 78 ) , 10 box binding protein ( XBP ) 1 , pancreatic ER kinase ( PERK ) , eukaryotic initiation factor 2 ( eIF 2 ) alpha , and growth arrest and DNA damage ( GADD ) 34 . ^^^ Exposure of cells to insulin activated UPR , as evidenced by an increased expression of GRP 78 , XBP 1 , phosphorylated PERK ( p PERK ) , and p eIF2alpha . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| The present study addresses another aspect of the ER unfolded protein response , i . e . activation of protein kinase R like ER kinase ( PERK or pancreatic ER kinase ) , which phosphorylates eukaryotic translation initiation factor 2 alpha ( eIF2alpha ) , thereby generally suppressing translation and decreasing the protein load on a damaged ER . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| HCMV infection activated the eIF2alpha kinase PERK ; however , the amount of phosphorylated eIF2alpha was limited and translation attenuation did not occur . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| In contrast , we demonstrate that the PERK pathway , leading to inhibition of cap dependent translation , is mainly activated upon reperfusion , as shown by PERK and eIF2alpha phosphorylation . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Renal ischemia and reperfusion activates the eIF 2 alpha kinase PERK . ^^^ We further show that increased eIF 2 alpha ( P ) is accompanied by activation of the PKR like endoplasmic reticulum eIF 2 alpha kinase ( PERK ) . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK is responsible for the increased phosphorylation of eIF2alpha and the severe inhibition of protein synthesis after transient global brain ischemia . ^^^ To address the role of the eIF2alpha kinase RNA dependent protein kinase like endoplasmic reticulum kinase ( PERK ) in the reperfused brain , transgenic mice with a targeted disruption of the Perk gene were subjected to 20 min of forebrain ischemia followed by 10 min of reperfusion . ^^^ These data demonstrate that PERK is responsible for the large increase in phosphorylated eIF2alpha and the suppression of translation early in reperfusion after transient global brain ischemia . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| A significant response to ischemia identified in brain is stress to the endoplasmic reticulum ( ER ) , as indicated by PKR like endoplasmic reticulum eIF2alpha kinase ( PERK ) mediated phosphorylation of eIF2alpha . ^^^ Although treatment of cultured neuroblastoma 104 cells with the NO donor S nitroso N acetyl penicillamine ( SNAP ) activated PERK , administration of L NAME had no effect on PERK activation or eIF2alpha phosphorylation in organs following ischemia and reperfusion . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK ( eIF2alpha kinase ) is required to activate the stress activated MAPKs and induce the expression of immediate early genes upon disruption of ER calcium homoeostasis . ^^^ The eIF2alpha ( eukaryotic initiation factor 2alpha ) kinase PERK ( doublestranded RNA activated protein kinase like ER kinase ) is essential for the normal function of highly secretory cells in the pancreas and skeletal system , as well as the UPR ( unfolded protein response ) in mammalian cells . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| We have studied the activation of the UPR in VWM through the immunohistochemical expression of its upstream components PERK and phosphorylated eIF2alpha ( eIF2alphaP ) and combined immunohistochemical and Western blot analysis of the downstream effector proteins activating transcription factor 4 ( ATF 4 ) and C / EBP homologous protein ( CHOP ) in 4 VWM brains and 3 age matched controls . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Inactivation of ISR signaling by mutations in the ER kinase PERK and the translation initiation factor eIF2alpha or by a dominant negative PERK impairs cell survival under extreme hypoxia . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK and GCN 2 contribute to eIF2alpha phosphorylation and cell cycle arrest after activation of the unfolded protein response pathway . ^^^ Exposure of cells to endoplasmic reticulum ( ER ) stress leads to activation of PKR like ER kinase ( PERK ) , eukaryotic translation initiation factor 2alpha ( eIF2alpha ) phosphorylation , repression of cyclin D 1 translation , and subsequent cell cycle arrest in G 1 phase . ^^^ Herein , we demonstrate that repression of cyclin D 1 translation after UPR activation occurs independently of PERK , but it remains dependent on eIF2alpha phosphorylation . ^^^ Although phosphorylation of eIF2alpha in PERK / fibroblasts is attenuated in comparison with wild type fibroblasts , it is not eliminated . ^^^ The residual eIF2alpha phosphorylation correlates with the kinetics of cyclin D 1 loss , suggesting that another eIF2alpha kinase functions in the absence of PERK . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| We report that PERK activation and phosphorylation selectively enhance its affinity for the nonphosphorylated eIF 2 complex . ^^^ Our findings suggest a novel mechanism for eIF 2 recruitment by activated PERK and for unidirectional substrate flow in the phosphorylation reaction . . ^^^ Regulated phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 ( eIF2alpha ) by the endoplasmic reticulum ( ER ) stress activated protein kinase PERK modulates protein synthesis and couples the production of ER client proteins with the organelle ' s capacity to fold and process them . ^^^ Although it is dispensable for catalytic activity , PERK ' s kinase insert loop is required for substrate binding and for eIF2alpha phosphorylation in vivo . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Infection with these same strains decreased transcript and protein levels of P 58 ( IPK ) , the cellular inhibitor of the eukaryotic initiation factor 2alpha ( eIF2alpha ) kinases PKR and PERK . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Hypoxia has recently been shown to activate the endoplasmic reticulum kinase PERK , leading to phosphorylation of eIF2alpha and inhibition of mRNA translation initiation . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| As for PERK / eIF2alpha pathway , the activation of ER eIF2alpha kinase PERK was observed . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Celecoxib caused phosphorylation of eukaryotic translation initiation factor 2 kinase ( PERK ) and eukaryotic initiation factor 2alpha ( eIF2alpha ) and production of activating transcription factor ( ATF ) 4 mRNA . ^^^ These results suggest that the Ca2+ dependent activation of the PERK eIF2alpha ATF 4 pathway is involved in the upregulation of ER chaperones by celecoxib . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| When this occurs in the endoplasmic reticulum ( ER ) , a process known as unfolded protein response ( UPR ) is orchestrated for survival through activation of PERK eIF2alpha ( PERK : double stranded RNA activated protein kinase like ER kinase ; eIF2alpha : eucaryotic initiation factor 2alpha ) , ATFalpha ( ATFalpha : activating transcription factor 6 ) and inositol requiring 1 ( IRE 1 ) 10 box binding protein 1 ( XBP 1 ) signalings . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| PERK , an eIF2alpha kinase , is found to interact with wt and mutants of eIF2alpha in which the serine 51 or 48 residue is replaced by alanine or aspartic acid thereby suggesting that the phosphorylation site in the substrate is not important for interaction . ^^^ Fluorescence spectroscopic and fluorescence resonance energy transfer analyses reveal that the energy transfer occurs from PERK to eIF2alpha . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| However , bortezomib rapidly induced components of the proapoptotic / terminal UPR , including PERK , the ER stress specific eIF 2alpha kinase ; ATF 4 , an ER stress induced transcription factor ; and its proapoptotic target , CHOP / GADD153 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| ER stress related molecules PERK , eIF2alpha , ATF 6 , XBP 1 , BiP , CHOP , and caspase 12 were analyzed . ^^^ Arginine treatment also caused an early activation of ER stress , as indicated by phosphorylation of PERK and its downstream target eIF2alpha , ATF 6 translocation into the nucleus ( within 1 h ) , and upregulation of BiP ( within 4 h ) . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| In response to various cellular stress , eIF2alpha is phosphorylated by distinct protein kinases ( PKR , PERK , GCN 2 , and HRI ) , and this event results in protein translation shut down . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| The expression of ER stress related genes ( IRE 1 , ATF 6 , GRP 78 , eif2alpha , ATF 4 , PERK ) was studied by using in situ hybridization in different brain areas on post operative days 2 , 7 , 14 and 28 . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| The UPR transducer PERK , which launches the most immediate response to ER stress ( i . e . the transient attenuation of mRNA translation ) , and the downstream effector of PERK , eIF2alpha , were shown to be activated in AD . ^^^ We demonstrate that neither in sporadic nor in infectiously acquired or inherited human prion diseases can the activated forms of PERK and eIF2alpha be detected , except when concomitant neurofibrillary pathology is present ; whereas the distribution of phosphorylated PERK correlates with abnormally phosphorylated tau in AD . ^^^ The lack of prominent activation of the PERK eIF2alpha pathway in prion diseases suggests that , in contrast to AD , ER stress does not play a crucial role in neuronal death in prion disorders . . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| Hypoxia induces phosphorylation of the translation initiation factor eIF2alpha on Ser 51 via activation of the endoplasmic reticulum ( ER ) resident kinase PERK and that this modification is required for the rapid downregulation of global protein synthesis by this hypoxic stress . ^^^ PERK dependent phosphorylation of eIF2alpha is one component of the Unfolded Protein Response ( UPR ) , a coordinated program that promotes cell survival under conditions of ER stress . ^^^ Inactivation of PERK or eIF2alpha phosphorylation impairs cell survival under hypoxia , and transformed cells with inactivating PERK or eIF2alpha mutations form tumors in nude mice that are slower growing , and have higher levels of apoptosis in hypoxic areas compared to tumors with an intact UPR . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| The proapoptotic effects of PKR mediated eIF2alpha phosphorylation contrast with the anti apoptotic response upon activation of the PKR related endoplasmic reticulum eIF2alpha kinase , PERK . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| In primary cultures of rat cerebellar granule neurons ( CGNs ) , the ER stressor brefeldin A activated a discrete pathway involving the following : ( 1 ) stimulation of the ER resident kinase PERK , ( 2 ) enhanced phosphorylation of the translation initiation factor eIF2alpha , and ( 3 ) increased expression and nuclear localization of the transcription factor Gadd153 / CHOP . ^^^ |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q9NZJ5 and P05198 |
Pubmed |
SVM Score :0.0 |
| NA |
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