Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Preparations of the hemin controlled repressor ( HCR ) from rabbit reticulocytes contain 3 ' : 5 ' cyclic AMP independent protein kinase activity for the smallest subunit of the peptide initiation factor eIF 2 and for proteins of reticulocyte 40S ribosomal subunits . ^^^
Interacting proteins: Q9BQI3 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 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 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Eukaryotic protein synthesis initiation factor 2 ( eIF 2 ) can be phosphorylated on its alpha subunit by two well characterised protein kinases , termed the haem controlled repressor ( HCR ) and the double stranded RNA activated inhibitor ( dsI ) . ^^^ Limited tryptic digestion and subsequent cyanogen bromide treatment of rat liver eIF 2 phosphorylated by HCR yielded one major phosphopeptide . ^^^ The same major phosphopeptide was obtained from rabbit reticulocyte eIF 2 phosphorylated by HCR or dsI as judged by its behaviour on two dimensional mapping and reverse phase chromatography . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Pretreatment with the haem controlled repressor ( HCR ) reduced the rate of ternary complex formation by crude ( liver ) eIF 2 . ^^^ In contrast , complex formation by an almost homogeneous eIF 2 preparation was unaffected by HCR : sensitivity to HCR was however restored by a factor which catalyses exchange of guanine nucleotides bound to eIF 2 . . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The hemin controlled repressor ( HCR ) and casein kinase 2 phosphorylate the alpha and beta subunits of eIF 2 , respectively . ^^^ The apparent Km for eIF 2 with HCR and casein kinase 2 was determined to be in the range of 0 . 5 1 . 0 microM . ^^^ Using fully dephosphorylated eIF 2 , it was possible to show that the phosphorylation state of the beta subunit did not affect the apparent Km of either HCR or casein kinase 2 for eIF 2 . ^^^ Hemin acted as a noncompetitive inhibitor of HCR with respect to eIF 2 with an apparent Ki of 3 microM , while inhibition of casein kinase 2 by 2 , 3 DPG was competitive with respect to eIF 2 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Two mammalian enzymes , the haem controlled repressor ( HCR ) and the double stranded RNA activated inhibitor ( dsI ) , phosphorylate Ser 51 of the alpha subunit , thereby inhibiting the exchange of bound nucleotides on , and thus the recycling of , eIF 2 . ^^^ Mammalian HCR and dsI are shown to phosphorylate specifically Ser 51 of yeast eIF 2 alpha , whereas extracts from yeast cells do not . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 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: Q9BQI3 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The protein was free of endogenous eIF2alpha kinase activity and was rapidly phosphorylated by the eIF2alpha kinases HCR and PKR . ^^^ The variant eIF2alpha was not phosphorylated by either HCR or PKR , demonstrating that the kinases specifically phosphorylate the correct site in the recombinant protein even in the absence of the other two subunits of the protein . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Expression and activity of p 67 are induced during heat shock . p 67 , a cellular glycoprotein , protects eIF 2 alpha from phosphorylation by inhibitory kinases such as PKR and HCR . p 67 promoter contains heat shock element ( HSE ) . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The reticulocyte heme controlled repressor phosphorylates the alpha subunit of eIF 2 from both sea urchins and rabbit reticulocytes . ^^^ Since both heme controlled repressor and casein kinase 2 phosphorylate the alpha subunit of sea urchin eIF 2 caution should be exercised when interpreting the significance of eIF 2 ( alpha ) phosphorylation in sea urchins . . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The wild type and Ser 48 mutant proteins became extensively phosphorylated by eIF 2 kinases present in the reticulocyte lysate , and when additional heme controlled repressor or double stranded RNA activated kinase was present , phosphorylation of the proteins was enhanced . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In contrast to reticulocyte polypeptide chain initiation factor 2 ( eIF 2 ) , the Artemia factor retains activity in the presence of Mg2+ or after phosphorylation of its alpha subunit by rabbit reticulocyte heme controlled repressor ( Mehta , H . ^^^ Partial trypsin digestion of the alpha subunit of Artemia eIF 2 after phosphorylation by the heme controlled repressor generates a 4000 Mr phosphopeptide . ^^^ Since this kinase phosphorylates a site distinct from that recognized by the heme controlled repressor , and this phosphorylation does not alter the ability of Artemia eIF 2 to undergo nucleotide exchange , caution must be exercised when interpreting the significance of eIF 2 ( alpha ) phosphorylation in non mammalian cells . . ^^^
Interacting proteins: Q9BQI3 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 . ^^^ 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
However , if the eIF 2 has previously been phosphorylated by the reticulocyte heme controlled repressor , the 40S subunit induced inhibition can not be reversed by elimination of free GDP . ^^^
Interacting proteins: Q9BQI3 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Both wild type and Ser48Ala variant forms of the free 2 alpha subunit , further purified by MonoQ chromatography , are poor substrates for the heme regulated eIF 2 alpha kinase , HRI , but are good substrates for double stranded RNA activated inhibitor in vitro ; the Ser51Ala variant subunit is not phosphorylated by either kinase . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The inhibition of translation is due to the activation of a heme regulated protein kinase ( HRI ) which specifically phosphorylates the alpha subunit of the eukaryotic initiation factor eIF 2 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 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 . ^^^
Interacting proteins: Q9BQI3 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 . ^^^ 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Using gel retardation assays we found that PKC , cyclic AMP dependent protein kinase ( PKA ) and a haem regulated eIF 2 kinase ( HRI ) could activate NF kappa B in vitro , whereas casein kinase 2 was ineffective . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
During heme deficiency in reticulocyte lysates , the heme regulated protein synthesis inhibitor , HRI , phosphorylates the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 ) and thus inhibits protein synthesis . ^^^ The eIF 2 gamma subunit in the free form was isolated , and addition of this isolated gamma subunit to RF promoted significant ternary complex formation . ( 3 ) Purified HRI efficiently phosphorylated the alpha subunit in the three subunit eIF 2 . ^^^ The 67 kDa polypeptide apparently protected eIF 2 alpha subunit from HRI catalyzed phosphorylation but did not inhibit HRI activity . ^^^ 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: Q9BQI3 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The specificity of the heme regulated protein kinase ( HRI ) was investigated further by utilizing the isolated 38 , 000 Da subunit ( alpha subunit ) polypeptide of eIF 2 as the substrate . ^^^ Results show that HRI is incapable of phosphorylating the 38 , 000 Da subunit separated from the other two eIF 2 polypeptides . ^^^ Data suggest that the substrate specificity of HRI is determined by the quaternary structure assumed by the alpha subunit in association with the other two subunits in the eIF 2 holoprotein . . ^^^
Interacting proteins: Q9BQI3 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In heme deficiency , a heme regulated protein kinase ( HRI ) is activated that phosphorylates initiation factor eIF 2 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In reconstituted in vitro assay mixtures containing Mg2+ ( 0 . 25 0 . 5 mM ) , RF catalyzes the formation of the binary complex ( eIF 2 GDP ) but this effect is inhibited when eIF 2 is phosphorylated by the heme regulated kinase for the alpha subunit of eIF 2 ( HRI ) . ^^^
Interacting proteins: Q9BQI3 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 . ^^^ In addition , an active RF preparation contains excess alpha subunit of eIF 2 in the free and unphosphorylated form and this alpha subunit of eIF 2 is not phosphorylated by HRI and ATP . ^^^ This RF activity is inhibited as the alpha subunit in the RF preparation becomes phosphorylated by HRI and ATP in the presence of GDP ; ( b ) RF contains Co eIF 2 activity , which has dual functions : ( 1 ) stimulation of ternary complex formation by eIF 2 and ( 2 ) GDP displacement from eIF 2 10 GDP during ternary complex formation . ^^^ In the presence of HRI and ATP , Co eIF 2 but does not displace GDP from eIF 2 alpha ( P ) 10 GDP . . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In partial reactions , HRI phosphorylates the Mr 38 , 000 subunit ( alpha subunit ) of eukaryotic initiation factor 2 ( eIF 2 ) , which forms a ternary complex , Met tRNAf 10 eIF 2 10 GTP . ^^^ 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 . ^^^ It has been observed that a significant part of this Mr 38 , 000 polypeptide component in eIF 2 10 RF and almost the entire Mr 38 , 000 polypeptide component in RF remain unphosphorylated after prolonged incubation with HRI and ATP . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
At present , there are two distinct mammalian eIF 2 alpha kinases that have been cloned , the double stranded RNA dependent eIF 2 alpha kinase ( PKR ) and the heme regulated eIF 2 alpha kinase ( HRI ) . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Two mammalian eIF 2 kinases , the double stranded RNA dependent kinase ( PKR ) and heme regulated inhibitor kinase ( HRI ) , have been characterized by sequencing , revealing shared sequence and structural features distinct from other eukaryotic protein kinases . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The results are as follows : ( 1 ) Both hemin and p 67 inhibited HRI ( heme regulated protein synthesis inhibitor ) and dsI ( double stranded RNA activated protein synthesis inhibitor ) catalyzed phosphorylation of eIF 2 alpha subunit in vitro . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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 . ^^^ 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Activated HRI inhibits translation by catalyzing the phosphorylation of the alpha subunit of eukaryotic initiation factor eIF 2 . ^^^ 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
There are two mammalian eIF 2alpha kinases : the double stranded RNA dependent kinase ( PKR ) and heme regulated inhibitor kinase ( HRI ) , and the yeast GCN 2 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The heme regulated eukaryotic initiation factor 2alpha ( eIF 2alpha ) kinase ( HRI ) interacts with hsp 90 in situ in rabbit reticulocyte lysate ( RRL ) . ^^^ Incubation of HRI in heme deficient lysate resulted in the transformation of a portion of the HRI polypeptides into an active heme regulatable eIF 2alpha kinase that exhibited slower electrophoretic mobility . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The heme regulated eIF 2alpha kinase ( HRI ) is activated not only in heme deficient rabbit reticulocyte lysates ( RRL ) , but also in hemin supplemented RRL treated with heat shock , N ethylmaleimide ( MalNEt ) or heavy metal ions . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The increased eIF 2alpha phosphorylation is the result of activation by PQQ of the heme regulated eIF 2alpha kinase ( HRI ) . ^^^ The addition of PQQ to reticulocyte lysates activates HRI whereas addition of PQQ to purified HRI in vitro inhibits the autokinase and eIF 2alpha kinase activity of the HRI ; the inhibition of purified HRI by PQQ is observed both in the presence and absence of hemin . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The catalytic kinase domain possesses highest identities ( 34 37 % ) with eukaryotic initiation factor 2alpha ( eIF 2alpha ) kinases , especially haem regulated inhibitory ( HRI ) protein kinases . ^^^ Thus PfPK 4 appears to be the first protozoan protein kinase related to eIF 2alpha kinases and might be the first non mammalian HRI kinase . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The role of the heat shock cognate protein , Hsc 70 , in regulating the activity of the heme regulated eIF 2alpha kinase ( HRI ) in hemin supplemented rabbit reticulocyte lysate ( RRL ) in response to heat and oxidative stress was examined and compared with the effect of Hsc 70 on HRI activation in response to heme deficiency . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In heme deficient reticulocyte lysates , the alpha subunit of eukaryotic initiation factor 2 ( eIF 2alpha ) is phosphorylated due to the activation of the heme regulated eIF 2alpha kinase ( HRI ) . ^^^ 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 . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In mammals , the phosphorylation was shown to be carried out by eIF 2alpha kinases PKR and HRI . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The heme regulated eukaryotic initiation factor 2alpha ( eIF2alpha ) kinase ( heme regulated inhibitor ( HRI ) ) is activated by heme deficiency in reticulocytes and plays an important role in translational control in these cells . ^^^ Previously , HRI was cloned from rabbit reticulocytes and rat brain , but a heme regulated eIF2alpha kinase activity has only been purified from erythroid cells . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In this study , we have examined the heme regulation directly on the homogeneous heme regulated eIF 2alpha kinase ( HRI ) , which is activated during heme deficiency . ^^^ This HRI was an active autokinase and eIF 2alpha kinase , and its kinase activities were inhibited by submicromolar concentrations of hemin with an apparent Ki of 0 . 5 microM . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
PERK has a lumenal domain that is similar to the ER stress sensing lumenal domain of the ER resident kinase Ire 1 , and a cytoplasmic portion that contains a protein kinase domain most similar to that of the known eIF2alpha kinases , PKR and HRI . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The phosphorylation is carried out in part by three distinct eIF 2alpha kinases including mammalian double stranded RNA dependent eIF 2alpha kinase ( PKR ) and heme regulated inhibitor kinase ( HRI ) , and yeast GCN 2 . ^^^ In contrast to PKR or HRI , which are dependent on autophosphorylation for their kinase activity , a point mutation that replaced the conserved Lys 614 with an alanine completely abolished the eIF 2alpha kinase activity , whereas the mutant PEK was still autophosphorylated when expressed in Sf 9 cells . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
We studied the effect of staurosporine on two well characterised mammalian eIF 2alpha kinases , the heme regulated translational inhibitor ( HRI ) , and interferon inducible double stranded RNA activated protein kinase ( PKR ) . ^^^ In the presence of 0 . 25 microM staurosporine ( a concentration which completely inhibits a wide range of Ser / Thr protein kinases ) , the phosphorylation of eIF 2alpha by HRI and PKR was not inhibited . ^^^
Interacting proteins: Q9BQI3 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The mammalian kinases PKR and HRI and the yeast kinase GCN 2 specifically phosphorylate Ser 51 on the alpha subunit of the translation initiation factor eIF 2 . ^^^ In addition , both PKR and HRI were found to phosphorylate eIF2alpha S51Y and stimulate GCN 4 expression . ^^^ Isoelectric focusing analysis of eIF2alpha followed by detection using anti eIF2alpha and anti phosphotyrosine specific antibodies demonstrated that PKR and HRI phosphorylated eIF2alpha S51Y on Tyr in vivo . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Three mammalian eIF2alpha kinases have been identified : the interferon inducible double stranded RNA dependent kinase ( PKR ) , the heme regulated inhibitor ( HRI ) , and the very recently discovered PERK / PEK . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In heme deficiency , protein synthesis in reticulocytes is inhibited by activation of heme regulated alpha subunit of eukaryotic initiation factor 2alpha ( eIF 2alpha ) kinase ( HRI ) . ^^^ Met 2 and Met 3 underwent autophosphorylation and phosphorylated eIF 2alpha with a specific activity of approximately 50 % of that of the wild type HRI . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In heme deficiency , inhibition of protein synthesis correlates with the activation of heme regulated eIF 2alpha kinase ( HRI ) , which blocks the initiation of protein synthesis by phosphorylating eIF 2alpha . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
One of mammalian eIF 2alpha kinases is a heme regulated inhibitor kinase ( HRI ) , which is activated by heme deficiency and plays an important role in translational control . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In this report , we examined the effect of the diffusible gases nitric oxide ( NO ) and carbon monoxide ( CO ) on the activation of the heme regulated eIF2alpha kinase ( HRI ) in rabbit reticulocyte lysate . ^^^ We postulate that the regulation of HRI activity by diffusible gases may be of wider physiological significance , as we further demonstrate that NO generators increase eIF2alpha phosphorylation levels in NT 2 neuroepithelial and C2C12 myoblast cells and activate HRI immunoadsorbed from extracts of these non erythroid cell lines . . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
To identify kinases responsible for eIF2alpha phosphorylation [ eIF2alpha ( P ) ] during brain reperfusion , we induced ischemia by bilateral carotid artery occlusion followed by post ischemic assessment of brain eIF2alpha ( P ) in mice with homozygous functional knockouts in the genes encoding the heme regulated eIF2alpha kinase ( HRI ) , or the amino acid regulated eIF2alpha kinase ( GCN 2 ) . ^^^ A 10 fold increase in eIF2alpha ( P ) was observed in reperfused wild type mice and in the HRI / or GCN 2 / mice . ^^^ These data indicate that neither HRI nor GCN 2 are required for the large increase in post ischemic brain eIF2alpha ( P ) , and in conjunction with our previous report that eIF2alpha ( P ) is produced in the brain of reperfused PKR / mice , provides evidence that PERK is the kinase responsible for eIF2alpha phosphorylation in the early post ischemic brain . . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In heme deficient reticulocytes , protein synthesis is inhibited due to the activation of heme regulated eIF2alpha kinase ( HRI ) . ^^^ Additional multiple autophosphorylation in the second stage is required for the formation of stable dimeric HRI ( species 2 ) with eIF2alpha kinase activity that is regulated by heme . . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
We have investigated the role of heme regulated inhibitor ( HRI ) , a heme regulated eIF2alpha kinase , in stress responses of erythroid cells . ^^^ HRI is the only eIF2alpha kinase activated by arsenite in erythroid cells , since HRI null cells do not induce eIF2alpha phosphorylation upon arsenite treatment . ^^^ HRI is also the major eIF2alpha kinase responsible for the increased eIF2alpha phosphorylation upon heat shock in erythroid cells . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
We establish that HRI , which is expressed predominantly in erythroid cells , regulates the synthesis of both alpha and beta globins in red blood cell ( RBC ) precursors by inhibiting the general translation initiation factor eIF 2 . ^^^ Heme regulated eIF2alpha kinase ( HRI ) is required for translational regulation and survival of erythroid precursors in iron deficiency . ^^^ Here , we report on the targeted disruption of the gene encoding the heme regulated eIF2alpha kinase ( HRI ) in mice . ^^^
Interacting proteins: Q9BQI3 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: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The heme regulated eIF2alpha kinase ( HRI ) phosphorylates the alpha subunit of the translation initiation factor 2 , which plays an important role in translational regulation during heme deficiency . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
One member of the eIF2alpha kinase family , heme regulated inhibitor kinase ( HRI ) , is activated under heme deficient conditions and blocks protein synthesis , principally globin , in mammalian erythroid cells . ^^^ The two HRI related kinases , named Hri1p and Hri2p , exhibit autokinase and kinase activity specific for Ser 51 of eIF2alpha , and both activities were inhibited in vitro by hemin , as previously described for mammalian HRI . ^^^ These results demonstrate that HRI related enzymes are not unique to vertebrates and suggest that these eIF2alpha kinases are important participants in diverse stress response pathways in some lower eukaryotes . . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Eukaryotic cells express a family of eukaryotic translation initiation factor 2 alpha ( eIF2alpha ) kinases ( eg , PKR , PERK PEK , GCN 2 , HRI ) that are individually activated in response to distinct types of environmental stress . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Autophosphorylation of threonine 485 in the activation loop is essential for attaining eIF2alpha kinase activity of HRI . ^^^ In heme deficiency , protein synthesis is inhibited by the activation of the heme regulated eIF2alpha kinase ( HRI ) through its multiple autophosphorylation . ^^^ Most importantly , autophosphorylation of Thr 485 , but not Thr 483 , was essential for attaining eIF2alpha kinase activity of HRI . ^^^ In addition , autophosphorylation of Thr 485 was necessary for arsenite induced activation of the eIF2alpha kinase activity of HRI , while autophosphorylation at Thr 483 was not required for activation by arsenite . ^^^ Collectively , our results demonstrate that autophosphorylation of Thr 485 is essential for the hyperphosphorylation and activation of HRI and is required for the acquisition of the eIF2alpha kinase activity . . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In this report , crystal structures of protein kinases were used to guide the dissection of two kinases [ the Src family tyrosine kinase , Lck , and the heme regulated eIF2alpha kinase ( HRI ) ] , and the association of Hsp 90 and Cdc 37 with these constructs was assessed . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In this report , we examine the structure function relationships that regulate the interaction of Cdc 37 with Hsp 90 and with an Hsp 90 dependent kinase , the heme regulated eIF2alpha kinase ( HRI ) . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The heme regulated eukaryotic initiation factor 2alpha ( eIF2alpha ) kinase ( HRI ) regulates the initiation of protein synthesis in reticulocytes . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
We have used human cell lines , namely , K 562 and HeLa cells as model systems in understanding the mechanism of lead toxicity and heat shock , that may be mediated by the heme regulated eIF 2alpha kinase which is also called the heme regulated inhibitor ( HRI ) . ^^^ Further , in vitro eIF 2alpha kinase assay indicated a two to three fold increase in HRI kinase activity during lead toxicity in K 562 cells . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Novobiocin specifically inhibited the maturation of the heme regulated eIF2alpha kinase ( HRI ) in a concentration dependent manner . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In this report we find that in addition to two previously described eIF 2 kinases related to mammalian HRI , designated Hri1p and Hri2p , the yeast Schizosaccharomyces pombe expresses a third eIF 2 kinase , a Gcn2p ortholog . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Heme regulated eIF2alpha kinase ( HRI ) controls protein synthesis by phosphorylating the alpha subunit of eukaryotic translational initiation factor 2 ( eIF2alpha ) . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
The heme regulated inhibitor of protein synthesis ( HRI ) regulates translation through the phosphorylation of the alpha subunit of eukaryotic initiation factor 2 ( eIF 2 ) . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
RESULTS : Differential mRNA display identified the gene heme regulated inhibitor eukaryotic initiation factor 2 alpha kinase ( HRI eIF 2a kinase ) in the lacrimal gland , the expression of which was reduced in the denervated lacrimal gland . ^^^ The sequenced fragment from differential display showed 94 % identity to rabbit HRI eIF 2a kinase . ^^^ The decreased expression of HRI eIF 2a kinase was confirmed by Northern and Western blots , and measurement of HRI eIF 2a kinase phosphorylation activity in the lacrimal gland after ablation of sensory neurons showed that it was significantly decreased compared with that of normal and control lacrimal glands . ^^^ CONCLUSIONS : The results suggest that loss of sensory innervation has a role in the lacrimal gland , contributing to the expression of HRI eIF 2a kinase , a pivotal negative regulator of protein synthesis . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
In response to various cellular stress , eIF2alpha is phosphorylated by distinct protein kinases ( PKR , PERK , GCN 2 , and HRI ) , and this event results in protein translation shut down . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
Heme regulated eIF2alpha kinase [ heme regulated inhibitor ( HRI ) ] plays a critical role in the regulation of protein synthesis by heme iron . ^^^ Study of the kinetics showed that the HRI kinase reaction follows classical Michaelis Menten kinetics with respect to ATP but sigmoidal kinetics and positive cooperativity between subunits with respect to the protein substrate ( eIF2alpha ) . ^^^
Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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Interacting proteins: Q9BQI3 and P05198	Pubmed	SVM Score :0.0
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