| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Previously , we have reported an age related increase in the activity of eEF 2 kinase ( BBRC , 192 , 1210 , 1993 ) . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| A novel method to identify protein kinase substrates : eEF 2 kinase is phosphorylated and inhibited by SAPK4 / p38delta . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| In brain and liver from hibernators , eEF 2 kinase activity was increased relative to that of active animals . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| BDNF induced phosphorylation of eEF 2 kinase ( Ser 366 ) , as well as decreased its kinase activity . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| A cDNA from rat skeletal muscle encoding calcium / calmodulin dependent eukaryotic elongation factor 2 kinase ( eEF 2K ) has been cloned and sequenced , and the amino acid sequence of the protein has been deduced . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The increase in eEF 2 phosphorylation was a consequence of the activation of eEF 2 kinase ( eEF 2K ) , which is a Ca2+ / calmodulin dependent kinase . eEF 2K was shown to be essentially inactive at less than 0 . 1 microM free Ca2+ when measured in cell free extracts . ^^^ We also show that the phosphorylation of eEF 2 and the activity of eEF 2K are insulin regulated in adipocytes . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Removal of approximately 130 residues from the C terminus of eEF 2K completely abolished autokinase activity ; however , removal of only 19 residues inhibited eEF 2 kinase activity but not autokinase activity , suggesting that a short region at the C terminal end may be important in interacting with eEF 2 . ^^^ A number of elongation factor 2 kinase ( eEF 2K ) mutants were constructed to investigate features of this kinase that may be important in its activity . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| TS 2 inhibited ATP or eEF 2 binding to eEF 2K in a competitive or non competitive manner , respectively . ^^^ In a multiple protein kinase assay using a postnuclear fraction of 5 src transformed NIH3T3 cells , 4 ethyl 4 hydroxy 2 p tolyl 5 , 6 dihydro 4H 1 , 3 selenazine ( TS 2 ) and 4 hydroxy 6 isopropyl 4 methyl 2 p tolyl 5 , 6 dihydro 4H 1 , 3 selenazine ( TS 4 ) exhibited selective inhibitory activity against eukaryotic elongation factor 2 kinase ( eEF 2K ) over protein kinase A ( PKA ) , protein kinase C ( PKC ) and protein tyrosine kinase ( PTK ) . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Elongation factor 2 kinase ( eEF 2K ) , also known as calmodulin dependent protein kinase 3 , is a member of the calmodulin mediated signaling pathway that links activation of cell surface receptors to cell division . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Elongation factor 2 kinase ( eEF 2K ) is a Ca ( 2+ ) / calmodulin dependent protein kinase that is highly specific for eukaryotic elongation factor 2 . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Elongation factor 2 kinase ( eEF 2K ) is a Ca ( 2+ ) / calmodulin dependent protein kinase that phosphorylates and inactivates eEF 2 and that can regulate the rate of protein synthesis at the elongation stage . ^^^ Kinetic studies demonstrate that the pH does not affect the K ( M ) for ATP or eEF 2 and activation of eEF 2K at acidic pH is due to an increase in 5 ( max ) . ^^^ Elongation factor 2 kinase ( eEF 2K ) is a Ca ( 2+ ) / calmodulin dependent protein kinase that phosphorylates and inactivates eEF 2 and that can regulate the rate of protein synthesis at the elongation stage . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| We recently demonstrated the activity of a class of histidine kinase inhibitors against a mammalian enzyme , elongation factor 2 kinase ( eEF 2K ) , and the effect of these compounds on cancer cell viability ( Arora et al . , 2003 ) . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The eEF 2 kinase activity was determined in the presence of an excess of the substrate , i . e . , non limiting concentrations of eEF 2 . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Among the various modifications of elongation factors , phosphorylation of eEF 2 by the specific Ca2+calmodulin dependent eEF 2 kinase is the best studied and perhaps the most important mechanism of regulation of elongation rate . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Reactivation of the eEF 2 kinase is associated with the phosphorylation of this protein . ^^^ Conventional preparations of HSP 90 contain an inactive eEF 2 kinase that could be activated after dephosphorylation and phosphorylation by the catalytic subunit of cAMP dependent protein kinase . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Elongation factor 2 ( eEF 2 ) is a 100 kD protein that catalyzes the ribosomal translocation reaction , resulting in the movement of ribosomes along mRNA . eEF 2 is the target for a very specific Ca2+ / calmodulin dependent eEF 2 kinase . ^^^ Elongation factor 2 ( eEF 2 ) is a 100 kD protein that catalyzes the ribosomal translocation reaction , resulting in the movement of ribosomes along mRNA . eEF 2 is the target for a very specific Ca2+ / calmodulin dependent eEF 2 kinase . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The sites in eukaryotic elongation factor eEF 2 phosphorylated by the Ca2+ / calmodulin dependent eEF 2 kinase in vitro have been identified . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Phosphorylation of translation elongation factor 2 ( eEF 2 ) by a specific Ca2+ / calmodulin dependent eEF 2 kinase plays an important role in the regulation of protein synthesis in mammalian cells . ^^^ We show here that an eEF 2 kinase similar to the mammalian enzyme is present in tissues of the amphibian Xenopus laevis . ^^^ We investigated changes in the activity of eEF 2 kinase in extracts of Xenopus oocytes at different stages of oogenesis . ^^^ The eEF 2 kinase activity was constant from stage 1 to stage 4 of oogenesis , but dramatically decreased after stage 4 . ^^^ Extracts of fully grown stage 6 oocytes showed no eEF 2 kinase activity . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| During differentiation the activity of the eEF 2 kinase is gradually reduced and reaches 10 % of that found in undifferentiated cells 5 days after the onset of differentiation . ^^^ However , the differentiated cells showed a dramatic decrease in the specific activity of the eEF 2 kinase . ^^^ The results show that the cellular content of eEF 2 varies with the rate of proliferation and that the activity of the eEF 2 kinase is high in undifferentiated proliferating cells and decreases upon differentiation even under conditions of an unaltered growth rate . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Interaction of the calcium and calmodulin regulated eEF 2 kinase with heat shock protein 90 . ^^^ Analysis of the bound material showed that the eEF 2 kinase was bound to the immunoadsorbent together with hsp 90 . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| In this paper , we establish the presence of Ca2+ / calmodulin dependent kinase 3 or eEF 2 kinase in these oocytes and describe how the protein synthesis inhibitor emetine is able to release them from the metaphase block . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The elongation factor 2 ( eEF 2 ) is selectively phosphorylated by the eEF 2 kinase ( calmodulin dependent kinase 3 ) . ^^^ By contrast , the eEF 2 kinase is rather resistant towards the potent but non selective protein kinase inhibitor staurosporine ( IC 50 > 50 microM ) and thus can be differentiated from most other protein kinases that are suppressed by staurosporine in the nM range . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| It maximally incorporated about 1 mol of phosphate / mol of eEF 2 kinase . ^^^ The Km of eEF 2 kinase for PKA was calculated to be 7 microM . ^^^ Phosphorylation of eEF 2 kinase by PKA induced calcium independent activity which amounted to 40 50 % of the total activity measured in the presence of calcium . ^^^ Furthermore , the level of calcium independent activity induced by phosphorylation by PKA was similar to that induced by the calcium stimulated autophosphorylation of eEF 2 kinase . ^^^ Phosphopeptide mapping of eEF 2 kinase labelled by autophosphorylation and by PKA revealed a number of common phosphopeptides . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| In this report , we show that eEF 2 from a cell line derived from the insect , Spodoptera frugiperda , is a substrate for mammalian eEF 2 kinase and that phosphorylation is Ca ( 2+ ) dependent . ^^^ However , we were unable to detect an eEF 2 kinase in Spodoptera cells . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The eEF 2 kinase could phosphorylate a synthetic peptide based on residues 49 60 of eEF 2 ( RAGETRFTDTRK ) , albeit only at a very low rate , and with a very high Km , compared to eEF 2 itself . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Here we show that , in Chinese hamster ovary cells expressing the human insulin receptor , insulin causes decreased phosphorylation of elongation factor eEF 2 and that this is associated with stimulation of the rate of peptide chain elongation . eEF 2 is phosphorylated by a very specific Ca 2+ / calmodulin dependent protein kinase ( eEF 2 kinase ) causing its complete inactivation . ^^^ The decrease in eEF 2 phosphorylation induced by insulin reflects a fall in eEF 2 kinase activity . ^^^ Rapamycin , a macrolide immunosuppressant which blocks the signalling pathway leading to the stimulation of the 70 / 85 kDa ribosomal protein S 6 kinases , substantially blocks the activation of elongation , the fall in eEF 2 phosphorylation and the decrease in eEF 2 kinase activity , suggesting that p7O S 6 kinase ( p70s6k ) and eEF 2 kinase may tie on a common signalling pathway . ^^^ Wortmannin , an inhibitor of phosphatidylinositide 3 OH kinase , had similar effects . eEF 2 kinase was phosphorylated in vitro by purified p70s6k but this had no significant effect on the in vitro activity of eEF 2 kinase . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Elongation factor 2 kinase : immunological evidence for the existence of tissue specific isoforms . eEF 2 kinase is a ubiquitous Ca2+ / calmodulin dependent protein kinase that is specific for protein synthesis elongation factor 2 ( eEF 2 ) . ^^^ This study describes an improved procedure for the purification of eEF 2 kinase from rabbit reticulocyte lysate . ^^^ The eEF 2 kinase preparation was used to raise polyclonal antibodies , which immunoprecipitated eEF 2 kinase protein and activity from rabbit reticulocyte lysate . ^^^ However , there was no immunoreactivity in extracts of rabbit or bovine liver or rabbit kidney despite the presence of abundant eEF 2 kinase activity in these tissues . ^^^ Exposure of PC 12 cells to nerve growth factor ( NGF ) resulted in rapid down regulation of eEF 2 kinase activity and a decrease in immunoreactivity . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Here we have examined in cortical neurons in culture the regulation by glutamate of phosphorylation of eukaryotic elongation factor 2 ( eEF 2 ) by eEF 2 kinase , a Ca2+ / calmodulin dependent enzyme . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| We cloned and sequenced the human , mouse , rat , and Caenorhabditis elegans eukaryotic elongation factor 2 kinase ( eEF 2 kinase ) and found that with the exception of the ATP binding site , they do not contain any sequence motifs characteristic of the eukaryotic protein kinase superfamily . ^^^ Comparison of different eEF 2 kinase sequences reveals a highly conserved region of approximately 200 amino acids which was found to be homologous to the catalytic domain of the recently described myosin heavy chain kinase A ( MHCK A ) from Dictyostelium . ^^^ This suggests that eEF 2 kinase and MHCK A are members of a new class of protein kinases with a novel catalytic domain structure . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Peptide chain elongation can also be activated by insulin , and this is associated with the dephosphorylation and activation of elongation factor eEF 2 , probably as a consequence of the insulin induced reduction in eEF 2 kinase activity . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| L type Ca2+ channel activity of GH 3 pituitary cells , which are enriched in calmodulin dependent eEF 2 kinase , was manipulated such that the impact of [ Ca2+ ] 1 on eEF 2 phosphorylation and translational rate could be examined for up to 10 min without inhibiting initiation . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| This inhibition was also associated with increased phosphorylation of elongation factor eEF 2 ( which inhibits its activity ) and enhanced Ca2+ / calmodulin independent activity of eEF 2 kinase . ^^^ Previous work has shown that phosphorylation of eEF 2 kinase by cAMP dependent protein kinase ( cAPK ) in vitro induces such activator independent activity , and the present data show that such a mechanism can occur in intact cells to link physiological levels of cAPK activation with inhibition of protein synthesis . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| A reconstituted system composed of eEF 2 , recombinant eEF 2 kinase , calmodulin , and calcium was also unaffected by prothymosin alpha . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Insulin also caused inhibition of glycogen synthase kinase 3 , which lies downstream of PKB , and of eEF 2 kinase . ^^^ The phosphorylation of eEF 2 itself was also decreased by insulin , and this effect and the inactivation of eEF 2 kinase were attenuated by rapamycin . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Biol . 9 , R 43 R45 ] . eEF 2 kinase is a ubiquitous protein kinase that phosphorylates and inactivates eukaryotic translational elongation factor 2 , and thus can modulate the rate of polypeptide chain elongation during translation . eEF 2 was the only known substrate for eEF 2 kinase . ^^^ We demonstrate here that eEF 2 kinase can efficiently phosphorylate a 16 amino acid peptide , MH 1 , corresponding to the myosin heavy chain kinase A phosphorylation site in Dictyostelium myosin heavy chains . ^^^ This enabled us to develop a rapid assay for eEF 2 kinase activity . ^^^ To localize the functional domains of eEF 2 kinase , we expressed human eEF 2 kinase in Escherichia coli as a GST tagged fusion protein , and then performed systematic in vitro deletion mutagenesis . ^^^ We analyzed eEF 2 kinase deletion mutants for the ability to autophosphorylate , and to phosphorylate eEF 2 as well as a peptide substrate , MH 1 . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Adrenergic agonists increase phosphorylation of elongation factor 2 in cardiomyocytes without eliciting calcium independent eEF 2 kinase activity . ^^^ Phosphorylation of eEF 2 inhibits its activity , and protein synthesis was inhibited in ARVC concomitantly with increased eEF 2 phosphorylation . eEF 2 kinase activity in ARVC extracts was completely dependent upon Ca ( 2+ ) / calmodulin . ^^^ Instead , they increased maximal eEF 2 kinase activity . ^^^ Similar data were obtained when partially purified ARVC eEF 2 kinase was treated with cAMP dependent protein kinase in vitro . ^^^ These data suggest that ARVC possess a distinct isoform of eEF 2 kinase . . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| We have studied angiotensin 2 ( ANG 2 ) dependent regulation of eukaryotic elongation factor 2 ( eEF 2 ) , an essential component of protein translation required for polypeptide elongation , in rat neonatal cardiac myocytes . eEF 2 is fully active in its dephosphorylated state and is inhibited following phosphorylation by eEF 2 kinase . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Our recent studies have also identified the mechanism by which mTOR signalling regulates the phosphorylation of eEF 2 . eEF 2 kinase is phosphorylated by p 70 S6 kinase at Ser 366 ; this results in the inactivation of eEF 2 kinase , especially at low ( micromolar ) Ca concentrations . . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Insulin induces dephosphorylation of eEF 2 and inactivation of eEF 2 kinase , and these effects are blocked by rapamycin , which inhibits the mammalian target of rapamycin , mTOR . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| One such mechanism involves activation of mTOR ( Fig . 1 ) . mTOR controls a myriad of downstream effectors , including RNA polymerase 1 , S6K1 , 4E BP 1 , and eEF 2 kinase . ^^^ Finally , amino acids cause inhibition of the eEF 2 kinase , resulting in an increase in the proportion of eEF 2 in the active , dephosphorylated form . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| In this study , eEF 2 specific , Ca2+ / CaM dependent protein kinase 3 ( CaM PK 3 ) , also called eEF 2 kinase , was examined under oxidative stress and cell proliferation state using CHO cells . ^^^ The eEF 2 kinase activity was determined in the kinase buffer containing Ca2+ and CaM in the presence of eEF 2 and [ gamma 32P ] ATP . ^^^ The eEF 2 kinase activity in cell lysates was completely dependent upon Ca2+ and CaM . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Phosphorylation of elongation factor 2 ( eEF 2 ) by the highly specific eEF 2 kinase results in eEF 2 inactivation and , therefore , may regulate the global rate of protein synthesis in animal cells . ^^^ Cloning and sequencing of eEF 2 kinase led to the discovery of a new family of protein kinases , named alpha kinases , whose catalytic domains display no sequence homology to conventional eukaryotic protein kinases . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Previous work showed that stress activated protein kinase 4 ( SAPK 4 , also called p38delta ) inhibits eEF 2 kinase in vitro by phosphorylating Ser 359 , while ribosomal protein S 6 kinases inhibit eEF 2 kinase by phosphorylating Ser 366 [ Knebel , Morrice and Cohen ( 2001 ) EMBO J . 20 , 4360 4369 ; Wang , Li , Williams , Terada , Alessi and Proud ( 2001 ) EMBO J . 20 , 4370 4379 ] . ^^^ In the present study we have examined the effects of the protein synthesis inhibitor anisomycin and tumour necrosis factor alpha ( TNF alpha ) on the phosphorylation of eEF 2 kinase . ^^^ Ser 377 is probably a substrate of MAPKAP K2 / K3 ( mitogen activated protein kinase activated protein kinase 2 / kinase 3 ) in cells , because eEF 2 kinase is phosphorylated efficiently by these protein kinases in vitro and phosphorylation of this site , induced by TNF alpha and low ( but not high ) concentrations of anisomycin , is prevented by SB 203580 , which inhibits SAPK2a / p38 , their `` upstream ' ' activator . ^^^ Since the phosphorylation of Ser 377 does not inhibit eEF 2 kinase in vitro , our results suggest that anisomycin or TNF alpha inhibit eEF 2 kinase via the phosphorylation of Ser 359 . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Lastly , eEF 2 kinase , the kinase that phosphorylates eEF 2 , was activated in anoxic or AICA riboside treated hepatocytes . ^^^ Therefore , the activation of eEF 2 kinase by AMPK , resulting in the phosphorylation and inactivation of eEF 2 , provides a novel mechanism for the inhibition of protein synthesis . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Recent work has shown that the activity of eEF 2 kinase is regulated by MAP kinase signalling and by the nutrient sensitive mTOR signalling pathway , which serve to activate eEF 2 in response to mitogenic or hormonal stimuli . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| When using specific inhibitors of the eEF 2 kinase prior to forskolin treatment , we were able to inhibit the increased phosphorylation of eEF 2 . ^^^ Furthermore , inhibition of eEF 2 kinase prevented the forskolin mediated down regulation of cyclin D 3 . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Human recombinant eEF 2 kinase ( eEF2K ) was phosphorylated by AMPK in a time and AMP dependent fashion , and phosphorylation led to eEF2K activation , similar to that observed in extracts from ischemic hearts . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| On the basis of the predicted amino acid sequence of eEF 2 kinase deduced from the cloned cDNA , we hypothesized that inhibitors of prokaryotic histidine kinases might also inhibit the activity of eEF 2 kinase . ^^^ NH 125 inhibited eEF 2 kinase activity ( IC ( 50 ) = 60 nM ) in vitro , blocked the phosphorylation of eEF 2 in intact cells , and showed relative selectivity over other protein kinases : protein kinase C ( IC ( 50 ) = 7 . 5 microM ) , protein kinase A ( IC ( 50 ) = 80 microM ) , and calmodulin dependent kinase 2 ( IC ( 50 ) > 100 microM ) . ^^^ Forced overexpression of eEF 2 kinase in a glioma cell line produced 10 fold resistance to NH 125 . ^^^ In conclusion , these results suggest that identification of potent inhibitors of eEF 2 kinase may lead to the development of new types of anticancer drugs . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The kinase that phosphorylates and inhibits elongation factor 2 ( eEF 2 kinase ) is inactivated by insulin via mTOR . ^^^ Insulin decreases the ability of eEF 2 kinase to bind calmodulin , its essential activator , and this effect requires mTOR signalling and a novel phosphorylation site in eEF 2 kinase , Ser 78 . ^^^ Ser 78 is not phosphorylated by known components of the mTOR pathway implying the existence of novel mTOR regulated kinases that control eEF 2 kinase . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The rate of peptide chain elongation can be modulated through the phosphorylation of eukaryotic elongation factor ( eEF ) 2 , which inhibits its activity and is catalyzed by a specific calcium / calmodulin dependent protein kinase termed eEF 2 kinase . ^^^ Here we show that AMPK directly phosphorylates eEF 2 kinase , and we identify the major site of phosphorylation as Ser 398 in a regulatory domain of eEF 2 kinase . ^^^ AMPK also phosphorylates two other sites ( Ser 78 and Ser 366 ) in eEF 2 kinase in vitro . ^^^ We develop appropriate phosphospecific antisera and show that phosphorylation of Ser 398 in eEF 2 kinase is enhanced in intact cells under a range of conditions that activate AMPK and increase the phosphorylation of eEF 2 . ^^^ Although cardiomyocytes appear to contain a distinct isoform of eEF 2 kinase , it also contains a site corresponding to Ser 398 that is phosphorylated by AMPK in vitro . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Here we show that insulin decreases the ability of eEF 2 kinase to bind calmodulin in a rapamycin sensitive manner . ^^^ We identify a novel phosphorylation site in eEF 2 kinase ( Ser 78 ) that is located immediately next to its calmodulin binding motif . ^^^ Mutation of this site to alanine strongly attenuates the effects of insulin and rapamycin both on the binding of calmodulin to eEF 2 kinase and on eEF 2 kinase activity . ^^^ This site is not a target for known kinases in the mTOR pathway , e . g . , the S 6 kinases , implying that it is phosphorylated by a novel mTOR linked protein kinase that serves to couple hormones and amino acids to the control of translation elongation . eEF 2 kinase is thus a target for mTOR signaling independently of previously known downstream components of the pathway . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| At the same time these secretagogues reduced elongation factor 2 ( eEF 2 ) phosphorylation , the main factor known to regulate elongation , and increased the phosphorylation of the eEF 2 kinase . ^^^ Neither rapamycin , SB 202190 , PD 98059 nor calyculin A had an effect on CCK mediated eEF 2 kinase phosphorylation . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Eukaryotic elongation factor 2 ( eEF 2 ) mediates the translocation step of peptide chain elongation and is inhibited through phosphorylation by eEF 2 kinase . ^^^ In addition , p70S6 kinase can regulate protein synthesis by phosphorylating eEF 2 kinase or via phosphorylation of ribosomal protein S 6 . ^^^ We have recently shown that eEF 2 kinase is also controlled by phosphorylation by AMP activated protein kinase ( AMPK ) , a key regulator of cellular energy homeostasis . ^^^ Activation of AMPK also resulted in decreased p70S6 kinase phosphorylation and increased phosphorylation of eEF 2 , suggesting that inhibition of protein synthesis involves the eEF 2 kinase / eEF2 axis and / or the p70S6 kinase pathway . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Eukaryotic elongation factor 2 kinase ( eEF 2 kinase ) is a highly conserved calcium / calmodulin dependent enzyme involved in the regulation of protein translation and cell proliferation . ^^^ Rapid changes in the activity and abundance of eEF 2 kinase have been observed on growth stimulation , and increased enzyme activity is characteristic of malignant cell growth . ^^^ Therefore , we determined whether the ubiquitin proteasome pathway regulates the turnover of eEF 2 kinase . ^^^ We found that eEF 2 kinase was a relatively short lived protein with a half life of less than 6 hours . eEF 2 kinase was ubiquitinated in vivo as determined by coimmunoprecipitation and polyubiquitin affinity matrix . ^^^ Incubation of purified eEF 2 kinase with a source of ubiquitination enzymes ( rabbit reticulocyte lysate ) , purified ubiquitin , and ATP revealed the presence of increasing molecular weight species of ubiquitinated eEF 2 kinase . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Paradoxically , activation of eEF 2 kinase ( eEF2K ) , the only known kinase that regulates eEF 2 , was observed only at 12 hours after SCH 66336 treatment . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Levels of mTOR and its downstream targets 4E BP 1 , eEF 2 , and eEF 2 kinase in relationships with tau in Alzheimer ' s disease brain . ^^^ In the current study , levels of various translation control elements including total and phosphorylated ( p ) forms of mammalian target of rapamycin ( mTOR ) , eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) , eukaryotic elongation factor 2 ( eEF 2 ) , and eEF 2 kinase were investigated in relationship with tau in homogenates of the medial temporal cortex from 20 AD and 10 control brains . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Elongation factor 2 ( EF 2 ) is phosphorylated and inhibited by the eEF 2 kinase ( CaM kinase 3 ) ; the latter is inhibited by the S6K or Rsk . ^^^ Elongation factor 2 ( EF 2 ) is phosphorylated and inhibited by the eEF 2 kinase ( CaM kinase 3 ) ; the latter is inhibited by the S6K or Rsk . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The in vitro activity of skeletal muscle eEF 2 kinase was not altered by exercise indicating that the increased activity of eEF 2 kinase to eEF 2 is not mediated by covalent mechanisms . ^^^ However , skeletal muscle eEF 2 kinase was potently activated by Ca ( 2 ) ( + ) calmodulin in vitro , suggesting that the higher eEF 2 phosphorylation in working skeletal muscle is mediated by allosteric activation of eEF 2 kinase by Ca ( 2 ) ( + ) signalling via calmodulin . ^^^ Given that eEF 2 phosphorylation inhibits eEF 2 activity and mRNA translation , these findings suggest that the inhibition of protein synthesis in contracting skeletal muscle is due to the Ca ( 2 ) ( + ) induced stimulation of eEF 2 kinase . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Knockdown of eEF 2 phosphorylation using eEF 2 kinase siRNA abolished these cardioprotective effects of AICAR . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| In the present study , we demonstrate that both NMDA and metabolic impairment by 2 deoxyglucose or inhibitors of mitochondrial respiration inhibit protein synthesis in cortical neurons through the phosphorylation of eukaryotic elongation factor ( eEF 2 ) , without any change in phosphorylation of initiation factor eIF 2alpha . eEF 2 kinase may be activated both by Ca ( 2+ ) independent AMP kinase or by an increase in cytosolic Ca2+ . ^^^ Conversely , 2 deoxyglucose likely activates eEF 2 kinase through a process involving phosphorylation by AMP kinase . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Elongation factor 2 kinase ( eEF 2 kinase ) , also known as Ca ( 2+ ) / calmodulin dependent kinase 3 , regulates protein synthesis by controlling the rate of peptide chain elongation . ^^^ The activity of eEF 2 kinase is increased in glioblastoma and other malignancies , yet its role in neoplasia is uncertain . ^^^ Because eEF 2 kinase lies downstream of mTOR , we studied the role of eEF 2 kinase in autophagy using human glioblastoma cell lines . ^^^ Knockdown of eEF 2 kinase by RNA interference inhibited autophagy in glioblastoma cell lines , as measured by light chain 3 ( LC 3 ) 2 formation , acidic vesicular organelle staining , and electron microscopy . ^^^ In contrast , overexpression of eEF 2 kinase increased autophagy . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Insulin inactivates eEF 2 kinase by increasing its phosphorylation at several mTOR regulated sites . ^^^ Several key questions remain about , for example , the mechanisms by which mTOR controls 4E BP 1 and eEF 2 kinase and the control of ribosomal protein translation . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| This effect seems to be mediated by activation of eEF 2 kinase , a calcium / calmodulin dependent enzyme which specifically phosphorylates and blocks eEF 2 . ^^^ The results raise the possibility that NMDA receptor activation stimulates two different calmodulin dependent enzymes ( eEF 2 kinase and NOS ) reinforcing local NO production by increasing precursor availability together with NOS catalytic activity . . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Gene silencing of 4E BP 1 and eEF 2 kinase or TSC 2 confers resistance to hypoxia inhibition of protein synthesis in immortalized breast epithelial cells . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Purification and phosphorylation of elongation factor 2 kinase from rabbit reticulocytes . ^^^ Eukaryotic elongation factor 2 kinase has been purified to homogeneity from rabbit reticulocytes through a seven step procedure and has been identified as a protein with a molecular mass of approximately 103 kDa as judged by SDS / PAGE . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| The functionally mapped catalytic domain of MHCK A shows no detectable sequence similarity to known classes of eukaryotic protein kinases but shares substantial sequence similarity with a transcribed Caenorhabditis elegans gene and with the mammalian elongation factor 2 kinase ( calcium / calmodulin dependent protein kinase 3 ) . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| It is likely that the related segments of homology present in rat eukaryotic elongation factor 2 kinase and a putative nematode eukaryotic elongation factor 2 kinase also encode the catalytic domains of those enzymes . . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Activity and regulation by growth factors of calmodulin dependent protein kinase 3 ( elongation factor 2 kinase ) in human breast cancer . ^^^ Calmodulin dependent protein kinase 3 ( CaM kinase 3 , elongation factor 2 kinase ) is a unique member of the Ca2+ / CaM dependent protein kinase family . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| They include elongation factor 2 kinase , Dictyostelium myosin heavy chain kinases and many other protein kinases from diverse organisms , as revealed by various genome sequencing projects . ^^^ |
|
| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| To screen the compounds that inhibit protein kinases , we used an assay system in which activities of protein kinase A , protein kinase C , src family protein tyrosine kinases and eukaryotic elongation factor 2 kinase were simultaneously detected on a single gel for the cytoplasmic protein kinases . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| Another possible rapamycin sensitive target is the inactivation of eukaryotic elongation factor 2 kinase . ^^^ Eukaryotic elongation factor 2 kinase phosphorylates and inactivates eukaryotic elongation factor 2 , blocking translational elongation . ^^^ |
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| Interacting proteins: O00418 and P13639 |
Pubmed |
SVM Score :0.0 |
| In cells lacking TSC 2 , amino acid withdrawal still results in dephosphorylation of S6K1 , ribosomal protein S 6 , the eukaryotic initiation factor 4E binding protein , and elongation factor 2 kinase . ^^^ This likely involves the phosphorylation of the elongation factor 2 kinase by the AMP activated protein kinase . . ^^^ |
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