Affinage

EEF2K

Eukaryotic elongation factor 2 kinase · UniProt O00418

Length
725 aa
Mass
82.1 kDa
Annotated
2026-06-09
100 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EEF2K is an atypical Ca2+/calmodulin-dependent α-kinase that serves as a master brake on translational elongation by phosphorylating eEF2 at Thr56, lowering eEF2's ribosomal affinity and slowing A-to-P site translocation (PMID:22669845, PMID:21605678). CaM engages eEF2K mainly through its C-lobe in a Ca2+-tunable manner (PMID:27602990), and in contracting skeletal muscle this Ca2+/CaM input alone suppresses protein synthesis independently of AMPK (PMID:19188248). The kinase integrates stress and energy signals from many directions: genotoxic stress acts via AMPK phosphorylation of Ser398 followed by autophosphorylation-triggered SCF(βTrCP) degradation that permits elongation to resume (PMID:22669845); myostatin and other inputs feed through the AMPK–eEF2K–eEF2 axis (PMID:29024627); NF-κB (p65) transcriptionally represses eEF2K to relieve elongation blockade (PMID:31636182); and ER/oxidative stress and ribosome biogenesis defects converge on eEF2K to reprogram translation, drive autophagy, and tune apoptotic sensitivity by controlling short-lived proteins such as XIAP and c-FLIPL (PMID:19221463, PMID:23182879, PMID:24582807, PMID:25332393). Mechanistically, eEF2K-phosphorylated eEF2 locks vacant 80S ribosomes carrying SERBP1 into a splitting-resistant inactive state, defining a reservoir of dormant ribosomes (PMID:34815424). In the nervous system, eEF2K controls localized synaptic translation through Homer1b/c scaffolding under mTORC1 control, shapes the excitation/inhibition balance and seizure susceptibility, gates associative taste learning and adult neurogenesis, and couples elongation slowing to the integrated stress response and BDNF synthesis in pain signaling (PMID:22366775, PMID:27005990, PMID:32892352, PMID:32707059, PMID:39694034). Beyond elongation control, eEF2K acts as a protein kinase and signaling hub with non-eEF2 substrates: it directly binds and phosphorylates GSK3β at Ser9 to stabilize PD-L1 and protect cardiomyocytes, phosphorylates AURKA at Ser391 to drive triple-negative breast cancer, and promotes STAT3-driven SPP1 transcription and uORF-dependent PD-L1 translation, collectively supporting tumor progression and immune evasion (PMID:35347072, PMID:33094805, PMID:35184394, PMID:39950798, PMID:39708064). A kinase-independent function is also documented: in C. elegans, EFK-1 promotes starvation survival by upregulating DNA-repair transcription and suppressing ROS without changing eEF2 phosphorylation (PMID:39966347), paralleling roles in redox homeostasis and antioxidant defense across cancer and immune cells (PMID:40506255, PMID:40409701).

Mechanistic history

Synthesis pass · year-by-year structured walk · 32 steps
  1. 2009 High

    Established that Ca2+/calmodulin can drive eEF2K-dependent suppression of translation in a physiological tissue independently of AMPK, defining a dedicated Ca2+-sensing arm of elongation control.

    Evidence Ex vivo contracting fast-twitch muscle with pharmacological Ca2+ manipulation, eEF2K inhibition, and kinase-dead AMPK

    PMID:19188248

    Open questions at the time
    • Did not resolve how Ca2+/CaM input is integrated with other activating signals
    • Quantitative contribution to whole-body protein turnover unaddressed
  2. 2009 Medium

    Placed eEF2K within autophagy signaling and identified eIF2α and Ca2+ flux as context-dependent upstream activators during starvation versus ER stress.

    Evidence siRNA knockdown, phosphorylation assays, LC3-II autophagy readouts under two stress conditions

    PMID:19221463

    Open questions at the time
    • Direction of causality between eEF2K and autophagy machinery left partly correlative
    • Molecular link from eIF2α to eEF2K activation not defined
  3. 2011 High

    Demonstrated that recombinant human eEF2K is a catalytically competent monomer, enabling in vitro reconstitution of Ca2+/CaM-activated eEF2 phosphorylation.

    Evidence Recombinant purification, light scattering, kinetic in vitro kinase assays

    PMID:21605678

    Open questions at the time
    • No structural model of the kinase domain
    • Did not address regulatory phosphosite occupancy on the recombinant enzyme
  4. 2012 High

    Unified the eEF2K activation-and-disposal cycle during DNA-damage stress, showing AMPK-Ser398 activation followed by autophosphorylation-dependent SCF(βTrCP) degradation to time recovery of elongation.

    Evidence In vitro kinase assays, mutagenesis, Co-IP, ubiquitin-proteasome degradation assays, phosphosite mapping

    PMID:22669845

    Open questions at the time
    • Did not map all autophosphorylation sites controlling βTrCP recognition
    • Generality beyond genotoxic stress not tested
  5. 2012 High

    Provided in vivo genetic proof that eEF2-Thr56 phosphorylation is required for a specific form of cortical-dependent associative learning, linking elongation control to behavior.

    Evidence Kinase-inactive eEF2K knock-in mice, conditioned taste aversion behavior, MEMRI imaging

    PMID:22366775

    Open questions at the time
    • Did not identify which neuronal mRNAs depend on eEF2K for learning
    • Selectivity for associative versus incidental learning mechanistically unexplained
  6. 2012 Medium

    Identified DDIT4/REDD1 as an ER-stress transducer to eEF2K and assigned opposing autophagy outcomes to distinct phosphosites (Ser398 vs Ser366/Ser78).

    Evidence RNAi, phosphomutant constructs, autophagy/apoptosis assays

    PMID:23182879

    Open questions at the time
    • Kinases acting on Ser78/Ser366 in this context not fully defined
    • Single-lab phosphomutant interpretation
  7. 2014 High

    Defined eEF2K as an oxidative-stress sensor that tunes apoptotic threshold by downregulating short-lived survival proteins, with conserved roles in mouse and worm reproduction.

    Evidence eEF2K knockout mice and C. elegans genetics, protein synthesis and apoptosis assays, XIAP/c-FLIPL westerns

    PMID:24582807

    Open questions at the time
    • Whether selective loss of XIAP/c-FLIPL is due solely to global elongation slowing not fully resolved
    • Sensing mechanism for oxidative stress upstream of eEF2K undefined
  8. 2014 High

    Showed eEF2K can act upstream of AMPK-ULK1 to restrain autophagy in cancer cells, revealing bidirectional, context-dependent coupling to the AMPK axis.

    Evidence siRNA, autophagic flux assays, epistasis via AMPK/ULK1 knockdown

    PMID:24955726

    Open questions at the time
    • Mechanism by which eEF2K influences AMPK activity not defined
    • Tissue generality of upstream placement unknown
  9. 2014 Medium

    Connected eEF2K to translational reprogramming, showing ribosomal stress activates eEF2K to selectively favor TOP mRNA translation.

    Evidence Ribosomal stress induction, eEF2K inhibition, polysome profiling

    PMID:25332393

    Open questions at the time
    • Mechanism linking elongation slowing to TOP-mRNA selectivity unresolved
    • Single-lab pharmacological approach
  10. 2014 High

    Established active-site Cys146 as a non-conserved residue exploitable for reversible covalent eEF2K inhibition, informing selective inhibitor design.

    Evidence Two-step inhibition kinetics, active-site mutagenesis, molecular docking

    PMID:25224652

    Open questions at the time
    • No crystallographic confirmation of the thioimidate adduct
    • Cellular selectivity not fully profiled
  11. 2016 High

    Revealed transcriptional control of eEF2K, with NF-κB/p65 repressing eEF2K to stimulate elongation under inflammatory and infectious stimuli.

    Evidence Multiple NF-κB stimuli, pre-mRNA quantification, p65 transcription assays, westerns

    PMID:31636182

    Open questions at the time
    • Direct p65 occupancy at the eEF2K locus described but promoter elements not fully mapped
    • Physiological consequence for pathogen replication not quantified
  12. 2016 High

    Demonstrated that eEF2K shapes the excitation/inhibition balance by restraining GABAergic transmission, linking the kinase to seizure susceptibility.

    Evidence eEF2K knockout mice, electrophysiology, Synapsin 2b/GABAAR westerns, seizure models

    PMID:27005990

    Open questions at the time
    • Whether Synapsin 2b/α5-GABAAR changes are direct translational targets undefined
    • Pre- vs postsynaptic site of action not fully separated
  13. 2016 Low

    Provided structural rationale for Ca2+-tunable activation by mapping eEF2K binding to the CaM C-lobe.

    Evidence NMR of CaM-eEF2K interaction (reported via commentary)

    PMID:27602990

    Open questions at the time
    • Original structural data only described in a commentary abstract, details limited
    • No full-length kinase-CaM complex structure
  14. 2017 Medium

    Showed myostatin suppresses muscle protein synthesis exclusively through the AMPK-eEF2K-eEF2 axis at low doses, placing eEF2K downstream of a growth-restraining hormone.

    Evidence C2C12 myotubes, SUnSET synthesis assay, pathway-specific inhibitors

    PMID:29024627

    Open questions at the time
    • In vivo confirmation in muscle limited
    • Dose-dependence of mTOR involvement not fully mapped
  15. 2019 Medium

    Identified Homer1b/c as a scaffolding partner controlling eEF2K localization and synaptic local translation under mTORC1 regulation.

    Evidence Co-IP, mTORC1 inhibition, phosphomutant constructs, synthesis assays in neurons

    PMID:32892352

    Open questions at the time
    • Single Co-IP-based interaction without structural mapping
    • Ser396 phosphorylation effect on binding affinity not quantified
  16. 2020 High

    Established eEF2K as a translational activator of PD-L1 by relieving uORF-mediated repression, linking elongation control to immune checkpoint expression.

    Evidence Genetic eEF2K ablation, polyribosome profiling, uORF reporter assays, NK cytotoxicity

    PMID:33094805

    Open questions at the time
    • Mechanism by which eEF2K affects uORF reinitiation undefined
    • Interplay with elongation slowing not reconciled
  17. 2020 Medium

    Defined a reciprocal eEF2K-MEK1/2 interaction generating an ERK feedback loop that is disrupted by AMPK during nutrient deprivation to promote survival.

    Evidence Co-IP (eEF2K-MEK1/2), AMPK activation, cell viability assays

    PMID:32565934

    Open questions at the time
    • Single Co-IP without reciprocal structural validation
    • Whether interaction depends on kinase activity unknown
  18. 2020 Medium

    Showed SIRT1 promotes eEF2K-dependent cardiac autophagy under ER stress and that eIF2α physically associates with eEF2K upstream of its activation.

    Evidence Co-IP (eIF2α-eEF2K), siRNA, SIRT1 modulation, in vivo cardiac function

    PMID:32059483

    Open questions at the time
    • Functional consequence of eIF2α-eEF2K binding not mechanistically dissected
    • Single-lab in vivo model
  19. 2020 High

    Placed eEF2K downstream of physiological neurogenic stimuli, with eEF2K loss enhancing adult dentate neurogenesis and learning.

    Evidence Global and conditional eEF2K knockout mice, neurogenesis markers, behavior

    PMID:32707059

    Open questions at the time
    • Cell-autonomous vs niche effects on neural progenitors not fully separated
    • Translational targets driving neurogenesis unidentified
  20. 2021 High

    Provided structural and biochemical evidence that eEF2K-phosphorylated eEF2 locks vacant 80S ribosomes into a SERBP1-bound, splitting-resistant inactive state, defining a dormant ribosome reservoir.

    Evidence Cryo-EM, in vitro ribosome splitting, pharmacological eEF2K activation, sensory neuron p-body imaging

    PMID:34815424

    Open questions at the time
    • Physiological signals controlling reactivation of these ribosomes undefined
    • Quantitative fraction of cellular ribosomes in this state unknown
  21. 2021 High

    Demonstrated in vivo that eEF2K activity is strictly required for Rpl24-mutation-driven elongation suppression and colorectal tumor suppression.

    Evidence Rpl24 × eEF2K double-mutant mouse epistasis, polysome profiling, tumor assays

    PMID:34895463

    Open questions at the time
    • How Rpl24 mutation activates eEF2K not defined
    • Translatome changes mediating tumor suppression not enumerated
  22. 2022 High

    Identified GSK3β-Ser9 as a direct non-eEF2 substrate of eEF2K, linking the kinase to PD-L1 stabilization and immune evasion in melanoma.

    Evidence IP-MS, Co-IP, in vitro phosphorylation, in vivo melanoma model, flow cytometry

    PMID:35347072

    Open questions at the time
    • Whether GSK3β phosphorylation requires eEF2K kinase activity in all contexts not fully tested
    • Structural basis of eEF2K-GSK3β recognition unknown
  23. 2022 High

    Defined an eEF2K-STAT3(Tyr705)-SPP1 transcriptional axis promoting melanoma progression, extending eEF2K function to transcription factor signaling.

    Evidence RNA-seq, STAT3 ChIP on SPP1 promoter, rescue experiments, in vivo model

    PMID:35184394

    Open questions at the time
    • Mechanism by which eEF2K increases STAT3 Tyr705 phosphorylation undefined
    • Direct vs indirect link unresolved
  24. 2022 Medium

    Positioned eEF2K as a convergence node downstream of PI3K and MEK pathways mediating synergy of combined inhibition in AML.

    Evidence Phosphoproteomics, siRNA, pharmacological inhibition across 12 AML lines

    PMID:35513296

    Open questions at the time
    • Cell-model-specific effects limit generalizability
    • Direct upstream kinases on eEF2K in this context not mapped
  25. 2022 Medium

    Revealed a redox-homeostasis function whereby eEF2K inhibition raises ROS and sensitizes cancer cells to ferroptosis, distinct from canonical translation control.

    Evidence Pharmacological and siRNA eEF2K inhibition, ROS/ferroptosis assays, multiple cell lines

    PMID:40409701

    Open questions at the time
    • Molecular mediators connecting eEF2K to antioxidant defense undefined
    • Dependence on eEF2 phosphorylation not separated
  26. 2023 High

    Showed alphavirus nsP2 NTPase activity hijacks cAMP/PKA to activate eEF2K and induce host translational shut-off, a conserved viral strategy.

    Evidence SILAC phosphoproteomics, NTPase Walker mutants, cAMP/PKA analysis

    PMID:36848386

    Open questions at the time
    • How nsP2 NTPase activates cAMP/PKA not defined
    • Selectivity of host shut-off for viral vs host mRNAs unaddressed
  27. 2023 Medium

    Developed a molecular-glue degrader (compound C1) mapping its eEF2K binding residues and showing it enhances βTRCP-mediated degradation, validating eEF2K as a druggable target.

    Evidence Binding assays, docking, Co-IP (eEF2K-βTRCP), degradation and antitumor experiments, organoids

    PMID:38084501

    Open questions at the time
    • Structural confirmation of the ternary complex absent
    • Single-lab degradation mechanism
  28. 2024 High

    Demonstrated eEF2K couples elongation slowing in sensory neurons to the integrated stress response and BDNF synthesis to drive pain behavior.

    Evidence In vivo eEF2K KO/inhibition, ISR inhibition, Bdnf-selective translation blockade, ribosome coupling assays

    PMID:39694034

    Open questions at the time
    • Identity of the ribosome-coupled ISR sensor not fully defined
    • How BDNF translation is selectively induced unresolved
  29. 2024 Medium

    Showed eEF2K protects against doxorubicin cardiotoxicity by phosphorylating and inhibiting GSK3β to restore autophagy, a protective counterpart to its oncogenic GSK3β signaling.

    Evidence AAV/adenoviral overexpression and knockdown, autophagy imaging, GSK3β inhibitor rescue, in vivo DIC model

    PMID:39708064

    Open questions at the time
    • Tissue-specific outcome of GSK3β inhibition not reconciled with tumor context
    • Single-lab model
  30. 2024 Medium

    Defined an eEF2K-Nrf2-mitochondrial axis in NK cells, with TGFβ-induced eEF2K driving oxidative stress and immunosuppression, and eEF2K loss enhancing anti-tumor function.

    Evidence CRISPR eEF2K KO in NK cells, proteomics, functional assays, in vivo adoptive transfer

    PMID:40506255

    Open questions at the time
    • Mechanism linking eEF2K to Nrf2 signaling undefined
    • Dependence on canonical eEF2 phosphorylation not tested
  31. 2025 Medium

    Identified AURKA-Ser391 as a new eEF2K substrate, defining an eEF2K/AURKA/SOX8 axis that promotes triple-negative breast cancer.

    Evidence Proteomics, Co-IP, in vitro phosphorylation, mutagenesis, xenografts, organoids

    PMID:39950798

    Open questions at the time
    • Whether AURKA phosphorylation requires CaM-dependent eEF2K activation unknown
    • Relatively recent single-lab finding
  32. 2025 High

    Established a kinase-independent eEF2K function in C. elegans promoting starvation survival via DNA-repair transcription and ROS suppression, decoupling protective roles from eEF2 phosphorylation.

    Evidence efk-1 and kinase-dead mutants, RNA-seq, ROS and oxygen consumption assays, survival assays

    PMID:39966347

    Open questions at the time
    • Molecular mechanism of the kinase-independent activity undefined
    • Conservation of this noncanonical role in mammals untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How eEF2K balances its canonical eEF2-elongation brake against its expanding repertoire of direct protein substrates (GSK3β, AURKA) and kinase-independent functions remains unresolved.
  • No structure of full-length eEF2K or its substrate complexes
  • Determinants of substrate selection between eEF2 and non-eEF2 targets unknown
  • Mechanistic basis of kinase-independent roles uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0045182 translation regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005840 ribosome 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 3 R-HSA-5357801 Programmed Cell Death 1
Partners
AURKABTRC (ΒTRCP)CALM1EEF2EIF2AK / EIF2S1 (EIF2Α)GSK3BHOMER1MAP2K1 (MEK1/2)

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 eEF2K phosphorylates eEF2 on Thr56, decreasing eEF2's affinity for the ribosome and inhibiting translocation (A-to-P site movement), thereby slowing peptide chain elongation. In response to genotoxic stress, AMPK activates eEF2K by phosphorylating it on Ser398. Subsequently, eEF2K is degraded via the SCF(βTrCP) ubiquitin ligase through autophosphorylation on a canonical βTrCP-binding domain, enabling resumption of translation elongation during DNA damage checkpoint silencing. In vitro kinase assays, mutagenesis, co-immunoprecipitation, ubiquitin-proteasome degradation assays, phosphosite mapping Science signaling High 22669845
2009 In contracting fast-twitch skeletal muscle, eEF2K is activated downstream of Ca2+/calmodulin (CaM), leading to phosphorylation of eEF2 and partial suppression (~30–40%) of protein synthesis. This Ca2+-CaM-eEF2K-eEF2 signaling cascade operates independently of AMPK or changes in intracellular pH. Ex vivo muscle contraction, pharmacological Ca2+ manipulation, eEF2K inhibitor treatment, kinase-dead AMPK overexpression, protein synthesis rate measurement The Journal of physiology High 19188248
2009 eEF2K is required for autophagy signaling during nutrient starvation and ER stress. During starvation, eIF2α phosphorylation is required upstream of eEF2K activation and eEF2 phosphorylation. During ER stress, eEF2K-mediated eEF2 phosphorylation can occur partly through Ca2+ flux independently of eIF2α phosphorylation. siRNA knockdown, phosphorylation assays, autophagy readouts (LC3-II), pharmacological inhibitors Autophagy Medium 19221463
2010 TRPM7, via its kinase domain, promotes phosphorylation of eEF2 at Thr56 under Mg2+-limited conditions by influencing the abundance and phosphorylation state of eEF2K at Ser77. TRPM7 kinase does not directly phosphorylate eEF2 but acts through eEF2K. Cell-based phosphorylation assays, TRPM7 kinase-dead mutants, western blotting Cellular signalling Medium 21112387
2011 Recombinant human eEF2K expressed in E. coli is a monomer of ~85 kDa (by light scattering) that phosphorylates eEF2 in vitro with kinetic parameters comparable to the mammalian enzyme. eEF2K is activated by calcium and calmodulin. Recombinant protein purification, light scattering, in vitro kinase assay, kinetic analysis Protein expression and purification High 21605678
2012 eEF2K activity (eEF2 phosphorylation at Thr56) is essential for cortical-dependent associative taste learning. Kinase-inactive eEF2K knock-in (ki) mice with reduced eEF2 phosphorylation show attenuated conditioned taste aversion but normal incidental taste learning, and exhibit altered brain activation patterns (by MEMRI) during learning. Kinase-inactive knock-in mice, behavioral testing (conditioned taste aversion), manganese-enhanced MRI (MEMRI), western blotting Learning & memory High 22366775
2012 Under ER stress, eEF2K is required for autophagy induction. DDIT4 (REDD1) transduces ER stress signals to activate eEF2K. Phosphorylation of eEF2K at Ser398 promotes autophagy, while phosphorylation at Ser366 and Ser78 inhibits autophagy. Suppression of eEF2K aggravates ER stress and shifts cells toward apoptosis. RNAi knockdown, phosphomutant constructs, autophagy and apoptosis assays, western blotting Autophagy Medium 23182879
2014 eEF2K senses oxidative stress and rapidly downregulates short-lived antiapoptotic proteins XIAP and c-FLIPL by inhibiting global protein synthesis, rendering cells susceptible to apoptosis. Loss of eEF2K in mice reduces ovarian apoptosis and leads to accumulation of aberrant follicles; loss of eEF2K ortholog in C. elegans reduces germ cell death and worsens oocyte quality. eEF2K knockout mice, C. elegans genetics, protein synthesis assays, western blotting for XIAP and c-FLIPL, apoptosis assays Developmental cell High 24582807
2014 Silencing of eEF2K in colon cancer cells increases protein synthesis and activates the AMPK-ULK1 pathway, inducing autophagy independently of mTOR suppression. Knockdown of AMPK or ULK1 abolishes eEF2K silencing-induced autophagy, placing eEF2K upstream of AMPK-ULK1 in this context. siRNA knockdown, LC3-II western blot, LC3 dot accumulation, autophagic flux assays, genetic epistasis (AMPK/ULK1 knockdown) Autophagy High 24955726
2014 eEF2K regulates the expression of tissue transglutaminase (TG2), and the eEF2K/TG2 axis promotes cancer cell survival. Inhibition of eEF2K leads to caspase-independent apoptosis associated with induction of apoptosis-inducing factor (AIF). eEF2K protein is degraded through the ubiquitin-proteasome pathway upon rottlerin treatment. siRNA knockdown, overexpression, western blotting, apoptosis assays (AIF, caspase), ubiquitin-proteasome pathway inhibitors Apoptosis Medium 24193916
2014 Ribosomal stress (ribosome biogenesis defect) activates the eEF2K-eEF2 pathway, inhibiting translation elongation. This causes a translational reprogramming in which TOP (terminal oligopyrimidine) mRNAs encoding ribosomal proteins are selectively recruited to polysomes, relatively increasing synthesis of TOP mRNA-encoded proteins. Ribosomal stress induction, eEF2K inhibition, polysome profiling, translation assays Nucleic acids research Medium 25332393
2014 A reversible covalent inhibition mechanism for eEF2K: the compound DFTD binds in two steps (fast binding followed by slow reversible inactivation). Molecular docking and mutagenesis indicate a nitrile group forms a reversible thioimidate adduct with the active-site Cys146, which is not conserved in related kinases. Kinetic analysis (two-step inhibition), active-site mutagenesis, molecular docking, chemoinformatics Chembiochem High 25224652
2016 NF-κB activation (by TNFα, HCMV infection, or dsDNA) represses eEF2K transcription through the p65 NF-κB subunit, reducing eEF2K pre-mRNA and protein levels, thereby decreasing eEF2 phosphorylation (Thr56) and stimulating translation elongation. NF-κB activation assays, eEF2K pre-mRNA quantification, pharmacological and genetic NF-κB modulation, p65 ChIP/transcription assays, western blotting Proceedings of the National Academy of Sciences of the United States of America High 31636182
2016 eEF2K activity negatively regulates GABAergic synaptic transmission in neurons. Loss of eEF2K increases GABAergic synaptic transmission by upregulating the presynaptic protein Synapsin 2b and α5-containing GABAA receptors, altering the excitation/inhibition balance and conferring resistance to epileptic seizures. eEF2K knockout mice, electrophysiology, western blotting for Synapsin 2b and GABAA receptor subunits, in vivo seizure models Cerebral cortex High 27005990
2017 Myostatin inhibits protein synthesis in skeletal muscle by activating AMPK, which in turn activates the eEF2K-eEF2 pathway. At low concentrations, myostatin suppresses protein synthesis exclusively through the AMPK-eEF2K-eEF2 axis without affecting mTOR. C2C12 myotube treatment with recombinant myostatin, SUnSET protein synthesis assay, western blotting, pharmacological pathway inhibitors Biochemical and biophysical research communications Medium 29024627
2019 eEF2K interacts with the scaffolding protein Homer1b/c, and this interaction is regulated by mTORC1-dependent phosphorylation of eEF2K at Ser396 (a known mTORC1 site). Homer1b/c binding controls eEF2K localization and affects rates of localized protein synthesis at synapses. Co-immunoprecipitation, pharmacological mTORC1 inhibition, phosphomutant constructs, protein synthesis assays in SH-SY5Y cells and mouse cortical neurons Journal of neurochemistry Medium 32892352
2020 Known physiological stimuli that enhance neurogenesis converge on the eEF2K/eEF2 pathway via AMPK in the dentate gyrus. eEF2K knockout in mature excitatory neurons of the dentate gyrus enhances adult neurogenesis and upregulates neurogenesis-related proteins, correlating with improved dentate gyrus-dependent learning. General and conditional eEF2K knockout mice, neurogenesis markers, behavioral testing, western blotting Current biology High 32707059
2020 SIRT1 promotes eEF2K/eEF2-dependent autophagy in cardiomyocytes under ER stress. eIF2α co-immunoprecipitates with eEF2K, and eIF2α knockdown reduces eEF2 phosphorylation, indicating eIF2α is required upstream of eEF2K activation in this cardiac context. Co-immunoprecipitation (eIF2α–eEF2K), siRNA knockdown, SIRT1 genetic/pharmacological modulation, autophagy assays in cardiac cells, in vivo cardiac function in SIRT1-deficient mice Cells Medium 32059483
2021 Phosphorylation of eEF2 (via eEF2K) suppresses translation elongation and is the principal mechanism by which Rpl24 mutation suppresses colorectal tumorigenesis in mice. Genetic inactivation of eEF2K in Rpl24 mutant mice completely restores elongation rate and protein synthesis, and abrogates the tumor-suppressive effect of the Rpl24 mutation, demonstrating that eEF2K activity is required for Rpl24-mediated tumor suppression. Genetic epistasis in mice (Rpl24 mutation × eEF2K inactivation), polysome profiling, protein synthesis rate measurement, tumor incidence/growth assays eLife High 34895463
2021 eEF2K phosphorylated eEF2 stabilizes vacant 80S ribosomes containing SERBP1 (in place of mRNA) and eEF2 in the acceptor site, as revealed by cryo-EM. Phosphorylated eEF2 associates with inactive ribosomes that resist splitting in vitro. eEF2K thus defines a population of inactive, recycling-resistant ribosomes and controls p-body abundance in sensory neurons. Cryo-electron microscopy, in vitro ribosome splitting assay, pharmacological eEF2K activation (nelfinavir), sensory neuron imaging, p-body quantification Nature communications High 34815424
2022 eEF2K directly binds to and phosphorylates GSK3β at Ser9, inactivating GSK3β and leading to stabilization and upregulation of PD-L1 protein in melanoma cells. Immunoprecipitation-mass spectrometry identified this interaction, and knockdown of eEF2K decreased PD-L1 and enhanced CD8+ T cell activity in vivo. Immunoprecipitation–mass spectrometry, Co-IP, in vitro phosphorylation assay, western blotting, in vivo mouse melanoma model, flow cytometry Journal for immunotherapy of cancer High 35347072
2020 eEF2K promotes translation of PD-L1 mRNA by attenuating the inhibitory effect of an upstream open reading frame (uORF) with a non-canonical CUG start codon in the PD-L1 5'-UTR. eEF2K depletion reduces PD-L1 mRNA association with translationally active polyribosomes and decreases PD-L1 protein levels. eEF2K ablation (genetic), polyribosome profiling, reporter assays for uORF activity, western blotting, NK cell cytotoxicity assays The Biochemical journal High 33094805
2022 eEF2K upregulates phosphorylation of STAT3 at Tyr705, which binds the SPP1 promoter and enhances SPP1 transcription to facilitate melanoma progression. Re-expression of SPP1 rescues the inhibitory effect of eEF2K silencing, and inhibition of SPP1 or STAT3 abolishes eEF2K-driven effects. RNA-seq, ChIP assay (STAT3 binding to SPP1 promoter), siRNA/overexpression, rescue experiments, in vivo mouse model Clinical and translational medicine High 35184394
2023 Alphavirus nsP2 NTPase domain activates a cAMP/PKA signaling cascade, leading to activation of eEF2K and subsequent phosphorylation of eEF2 at Thr56 (>50-fold increase), causing translational shut-off. NTPase-dead mutations prevent this eEF2 phosphorylation. This mechanism is shared across Old and New World alphaviruses. Phosphoproteomics (SILAC + LC-MS/MS), NTPase Walker A/B mutants, cAMP/PKA pathway analysis, translation inhibition assays PLoS pathogens High 36848386
2024 In sensory neurons, painful stimuli activate eEF2K to repress peptide chain elongation. Attenuated elongation is sensed by a ribosome-coupled mechanism that triggers the integrated stress response (ISR). Both eEF2K and the ISR are required for pain-associated behaviors in vivo. This pathway simultaneously induces BDNF biosynthesis; selective blockade of Bdnf translation has analgesic effects. In vivo eEF2K knockout/inhibition behavioral studies, ISR inhibition, Bdnf mRNA-selective translation blockade, ribosome coupling assays in sensory neurons Molecular cell High 39694034
2025 eEF2K binds to and phosphorylates aurora kinase A (AURKA) at Ser391, a newly identified phosphorylation site that is critical for AURKA protein stability and kinase activity. eEF2K also positively regulates SOX8 mRNA and protein expression, constituting an eEF2K/AURKA/SOX8 axis promoting TNBC progression. Proteomic analysis, Co-IP/binding assay, in vitro phosphorylation assay, mutagenesis, overexpression/knockdown, in vivo xenograft, patient-derived organoids Advanced science Medium 39950798
2023 eEF2K compound C1 (molecular glue) selectively binds to eEF2K residues F8, L10, R144, C146, E229, and Y236 and promotes proteasomal degradation of eEF2K by increasing interaction between eEF2K and the ubiquitin E3 ligase βTRCP. Binding affinity assays, molecular docking, ubiquitin-proteasome degradation assays, Co-IP (eEF2K–βTRCP), in vitro and in vivo antitumor experiments, patient-derived organoids Advanced science Medium 38084501
2020 Under nutrient-replete conditions, eEF2K interacts with MEK1/2, creating a positive feedback loop via MEK1/2-ERK1/2-RSK-eEF2K signaling. Under acute nutrient deprivation, AMPK activation blocks the eEF2K-MEK1/2 interaction, thereby decreasing ERK1/2 activity and reducing G1/S transition to promote cell survival. Co-immunoprecipitation (eEF2K–MEK1/2), AMPK activation, western blotting, cell viability assays under nutrient deprivation Oncology letters Medium 32565934
2022 eEF2K phosphorylation/activity is a key convergence point downstream of both PI3K and MAPK/MEK pathways and mediates synergism when these pathways are co-inhibited. eEF2K activity was elevated in acute myeloid leukemia cell lines where PI3Ki + MEKi cotreatment is synergistic; siRNA or small-molecule inhibition of eEF2K reversed antiproliferative synergy in a cell-model-specific manner. LC-MS/MS phosphoproteomics, siRNA knockdown, pharmacological inhibition, 12 AML cell line analysis Molecular & cellular proteomics Medium 35513296
2016 NMR analysis of calmodulin (CaM) binding to eEF2K revealed that eEF2K interacts mainly with the C-lobe of CaM in a Ca2+-tunable manner, providing structural insight into the Ca2+-dependent regulation of eEF2K activity. NMR spectroscopy of CaM-eEF2K interaction (cited from a study referenced in PMID:27602990 commentary) Structure Low 27602990
2025 In C. elegans, EFK-1/eEF2K promotes starvation survival via a noncanonical, kinase-activity-independent pathway: it upregulates transcription of DNA repair pathways (NER, BER) and suppresses oxygen consumption and ROS production. eEF2 phosphorylation levels are unchanged in starved C. elegans, indicating this protective role is independent of the canonical eEF2 phosphorylation function. C. elegans genetics (efk-1 mutants), kinase-dead efk-1 mutants, RNA-seq, ROS measurement, oxygen consumption assay, survival assays Nature communications High 39966347
2024 eEF2K deletion in NK cells activates Nrf2-mediated antioxidant signaling, sustaining mitochondrial fitness and active metabolism. TGFβ in the tumor microenvironment exacerbates oxidative stress and immunosuppression by inducing eEF2K in NK cells. eEF2K-knockout NK cells show enhanced maturation, proliferation, cytotoxicity, and reduced exhaustion. CRISPR/Cas9 eEF2K KO in NK cells, proteomic analysis, functional NK cell assays, in vivo mouse melanoma model, adoptive transfer of KO NK92 cells Cancer immunology research Medium 40506255
2022 eEF2K inhibition impairs cellular antioxidant defenses, leading to enhanced ROS accumulation and sensitizing cancer cells to ferroptosis inducers or glutathione depletion. This reveals a role of eEF2K in maintaining redox homeostasis beyond its canonical translation-regulatory function. Pharmacological inhibition (A484954) and siRNA knockdown of eEF2K, ROS measurement, ferroptosis and lipid peroxidation assays, multiple cancer cell lines European journal of pharmacology Medium 40409701
2017 eEF2K promotes glycolysis in rheumatoid arthritis fibroblast-like synoviocytes; knockdown of eEF2K suppresses TNF-α-induced NF-κB and AKT pathway activation, and lactate reverses the inhibitory effects of eEF2K knockdown on inflammation and migration, linking eEF2K-driven glycolysis to inflammatory signaling. siRNA knockdown, NH125 pharmacological inhibition, glucose uptake and lactate measurement, NF-κB/AKT western blotting, in vivo CIA mouse model Journal of inflammation research Medium 35300214
2024 eEF2K alleviates doxorubicin-induced cardiotoxicity by phosphorylating and inhibiting GSK3β, thereby improving autophagy dysfunction. eEF2K overexpression (via AAV) reduces cardiomyocyte death, while knockdown aggravates autophagy blockade; GSK3β inhibition rescues the effects of eEF2K knockdown. Adeno-associated virus overexpression, adenovirus overexpression in vitro, eEF2K knockdown, transmission electron microscopy for autophagy, mRFP-GFP-LC3 imaging, GSK3β inhibitor rescue, in vivo mouse DIC model Cell biology and toxicology Medium 39708064
2017 Fluoxetine induces autophagic cell death in TNBC cells through inhibition of eEF2K, which activates the AMPK-mTOR-ULK complex axis, promoting autophagy. MTT assay, electron microscopy, GFP-LC3 transfection, western blotting, siRNA, iTRAQ-based proteomics Cell proliferation Low 29094413
2021 eEF2K inhibition cooperated with glutamine starvation and synergized with glutaminase inhibitors to suppress TNBC cell growth. Combined eEF2K and 4EBP1 depletion affected the collagen-containing ECM pathway (e.g., COL1A1) and amino-acid transporter SLC7A5/LAT1, suggesting a regulatory loop via mTORC1. Genetic and pharmacological eEF2K inhibition, GLS1 inhibitor combination, 4EBP1 siRNA, proteomic analysis Scientific reports Low 33911160

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K. EMBO molecular medicine 95 25330770
2009 A Ca(2+)-calmodulin-eEF2K-eEF2 signalling cascade, but not AMPK, contributes to the suppression of skeletal muscle protein synthesis during contractions. The Journal of physiology 88 19188248
2012 Coupled activation and degradation of eEF2K regulates protein synthesis in response to genotoxic stress. Science signaling 87 22669845
2014 Silencing of EEF2K (eukaryotic elongation factor-2 kinase) reveals AMPK-ULK1-dependent autophagy in colon cancer cells. Autophagy 84 24955726
2014 Targeting elongation factor-2 kinase (eEF-2K) induces apoptosis in human pancreatic cancer cells. Apoptosis : an international journal on programmed cell death 77 24193916
2010 The channel-kinase TRPM7 regulates phosphorylation of the translational factor eEF2 via eEF2-k. Cellular signalling 71 21112387
2017 Fluoxetine induces autophagic cell death via eEF2K-AMPK-mTOR-ULK complex axis in triple negative breast cancer. Cell proliferation 70 29094413
2012 Integrated regulation of autophagy and apoptosis by EEF2K controls cellular fate and modulates the efficacy of curcumin and velcade against tumor cells. Autophagy 70 23182879
2018 Thymoquinone inhibits cell proliferation, migration, and invasion by regulating the elongation factor 2 kinase (eEF-2K) signaling axis in triple-negative breast cancer. Breast cancer research and treatment 66 29971628
2014 Germline quality control: eEF2K stands guard to eliminate defective oocytes. Developmental cell 58 24582807
2017 eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures. Cerebral cortex (New York, N.Y. : 1991) 57 27005990
2020 SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy. Cells 56 32059483
2017 Eukaryotic Elongation Factor 2 Kinase (eEF2K) in Cancer. Cancers 56 29186827
2012 Impaired associative taste learning and abnormal brain activation in kinase-defective eEF2K mice. Learning & memory (Cold Spring Harbor, N.Y.) 54 22366775
2016 eEF2K inhibition blocks Aβ42 neurotoxicity by promoting an NRF2 antioxidant response. Acta neuropathologica 48 27752775
2009 A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses. Autophagy 44 19221463
2022 eEF2K promotes PD-L1 stabilization through inactivating GSK3β in melanoma. Journal for immunotherapy of cancer 42 35347072
2020 Eukaryotic elongation factor-2 kinase (eEF2K) signaling in tumor and microenvironment as a novel molecular target. Journal of molecular medicine (Berlin, Germany) 42 32377852
2018 Elongation factor-2 kinase (eEF-2K) expression is associated with poor patient survival and promotes proliferation, invasion and tumor growth of lung cancer. Lung cancer (Amsterdam, Netherlands) 40 30268477
2017 eEF2K promotes progression and radioresistance of esophageal squamous cell carcinoma. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 40 28431753
2016 Pharmacological eEF2K activation promotes cell death and inhibits cancer progression. EMBO reports 39 27572820
2014 Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors. Bioorganic & medicinal chemistry 39 25047940
2021 Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance. Nature communications 38 34815424
2017 Design, synthesis, and biological evaluation of polo-like kinase 1/eukaryotic elongation factor 2 kinase (PLK1/EEF2K) dual inhibitors for regulating breast cancer cells apoptosis and autophagy. European journal of medicinal chemistry 38 29288948
2014 Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of terminal oligopyrimidine (TOP) mRNAs on polysomes. Nucleic acids research 38 25332393
2020 eEF2K enhances expression of PD-L1 by promoting the translation of its mRNA. The Biochemical journal 36 33094805
2022 EEF2K silencing inhibits tumour progression through repressing SPP1 and synergises with BET inhibitors in melanoma. Clinical and translational medicine 35 35184394
2014 Eukaryotic elongation factor-2 kinase (eEF2K): a potential therapeutic target in cancer. Apoptosis : an international journal on programmed cell death 35 25023961
2021 Roles of eukaryotic elongation factor 2 kinase (eEF2K) in neuronal plasticity, cognition, and Alzheimer disease. Journal of neurochemistry 30 34796967
2021 Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy. International journal of molecular sciences 28 33673713
2020 eEF2/eEF2K Pathway in the Mature Dentate Gyrus Determines Neurogenesis Level and Cognition. Current biology : CB 28 32707059
2020 Designing an eEF2K-Targeting PROTAC small molecule that induces apoptosis in MDA-MB-231 cells. European journal of medicinal chemistry 28 32717479
2020 Combined treatment of mitoxantrone sensitizes breast cancer cells to rapalogs through blocking eEF-2K-mediated activation of Akt and autophagy. Cell death & disease 28 33144562
2017 Design, synthesis and structure-activity relationship of a focused library of β-phenylalanine derivatives as novel eEF2K inhibitors with apoptosis-inducing mechanisms in breast cancer. European journal of medicinal chemistry 28 29202403
2015 MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma. Oncology letters 28 26893763
2011 Purification and characterization of tagless recombinant human elongation factor 2 kinase (eEF-2K) expressed in Escherichia coli. Protein expression and purification 27 21605678
2010 Inhibition of eEF2-K by thieno[2,3-b]pyridine analogues. Bioorganic & medicinal chemistry letters 27 20189382
2024 Enhanced NK cell activation via eEF2K-mediated potentiation of the cGAS-STING pathway in hepatocellular carcinoma. International immunopharmacology 23 38320351
2021 Rpl24 mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K. eLife 23 34895463
2017 Suppression of eEF-2K-mediated autophagy enhances the cytotoxicity of raddeanin A against human breast cancer cells in vitro. Acta pharmacologica Sinica 23 29239350
2017 Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis. Biochemical and biophysical research communications 22 29024627
2014 Reversible covalent inhibition of eEF-2K by carbonitriles. Chembiochem : a European journal of chemical biology 22 25224652
2019 Repression of eEF2K transcription by NF-κB tunes translation elongation to inflammation and dsDNA-sensing. Proceedings of the National Academy of Sciences of the United States of America 21 31636182
2018 Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 30522114
2019 Electroacupuncture Improves Synaptic Function in SAMP8 Mice Probably via Inhibition of the AMPK/eEF2K/eEF2 Signaling Pathway. Evidence-based complementary and alternative medicine : eCAM 20 31641367
2023 Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple-Negative Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 19 38084501
2020 Design, Synthesis, and Molecular Modeling Studies of Novel Coumarin Carboxamide Derivatives as eEF-2K Inhibitors. Journal of chemical information and modeling 19 32027127
2016 Mmu-miR-125b overexpression suppresses NO production in activated macrophages by targeting eEF2K and CCNA2. BMC cancer 16 27020049
2015 Using docking and alchemical free energy approach to determine the binding mechanism of eEF2K inhibitors and prioritizing the compound synthesis. Frontiers in molecular biosciences 16 25988177
2021 Inhibition of eEF2K synergizes with glutaminase inhibitors or 4EBP1 depletion to suppress growth of triple-negative breast cancer cells. Scientific reports 15 33911160
2021 Synergistic antitumor effect of resveratrol and sorafenib on hepatocellular carcinoma through PKA/AMPK/eEF2K pathway. Food & nutrition research 15 34776832
2023 The alphavirus nonstructural protein 2 NTPase induces a host translational shut-off through phosphorylation of eEF2 via cAMP-PKA-eEF2K signaling. PLoS pathogens 14 36848386
2022 miRNA-193b-5p Suppresses Pancreatic Cancer Cell Proliferation, Invasion, Epithelial Mesenchymal Transition, and Tumor Growth by Inhibiting eEF2K. Anti-cancer agents in medicinal chemistry 14 35718922
2024 eEF2K regulates pain through translational control of BDNF. Molecular cell 13 39694034
2022 eEF2K Activity Determines Synergy to Cotreatment of Cancer Cells With PI3K and MEK Inhibitors. Molecular & cellular proteomics : MCP 13 35513296
2022 Increased eEF2K Promotes Glycolysis and Aggressive Behaviors of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis. Journal of inflammation research 12 35300214
2016 Potentiation of Schaffer-Collateral CA1 Synaptic Transmission by eEF2K and p38 MAPK Mediated Mechanisms. Frontiers in cellular neuroscience 12 27826228
2022 Rescuing epileptic and behavioral alterations in a Dravet syndrome mouse model by inhibiting eukaryotic elongation factor 2 kinase (eEF2K). Molecular autism 11 34980259
2022 Novel etodolac derivatives as eukaryotic elongation factor 2 kinase (eEF2K) inhibitors for targeted cancer therapy. RSC medicinal chemistry 11 35923718
2025 Identification of a Novel Substrate for eEF2K and the AURKA-SOX8 as the Related Pathway in TNBC. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 39950798
2016 Integrative bioinformatics and proteomics-based discovery of an eEF2K inhibitor (cefatrizine) with ER stress modulation in breast cancer cells. Molecular bioSystems 10 26776155
2024 Targeting eukaryotic elongation factor 2 kinase (eEF2K) with small-molecule inhibitors for cancer therapy. Drug discovery today 9 39214495
2022 Discovery of New Inhibitors of eEF2K from Traditional Chinese Medicine Based on In Silico Screening and In Vitro Experimental Validation. Molecules (Basel, Switzerland) 9 35956836
2025 Fluoxetine-Conjugated Platinum(IV) Prodrugs Targeting eEF2K and Conquering Multidrug Resistance against Triple-Negative Breast Cancer. Journal of medicinal chemistry 8 40265570
2021 Eef2k is not required for fertility in male mice. Translational andrology and urology 8 34159079
2020 AMPK decreases ERK1/2 activity and cancer cell sensitivity to nutrition deprivation by mediating a positive feedback loop involving eEF2K. Oncology letters 8 32565934
2024 Structure-Activity Relationship Studies of Substituted 2-Phenyl-1,2,4-triazine-3,5(2H,4H)-dione Analogues: Development of Potent eEF2K Degraders against Triple-Negative Breast Cancer. Journal of medicinal chemistry 7 39208364
2023 eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design. Molecules (Basel, Switzerland) 7 36770760
2023 Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis. Pharmaceutical biology 7 37300283
2022 Homozygous knockout of eEF2K alleviates cognitive deficits in APP/PS1 Alzheimer's disease model mice independent of brain amyloid β pathology. Frontiers in aging neuroscience 7 36158543
2021 Endothelin-1 induces lipolysis through activation of the GC/cGMP/Ca2+/ERK/CaMKIII pathway in 3T3-L1 adipocytes. Biochimica et biophysica acta. Molecular and cell biology of lipids 7 34748972
2017 Calyxin Y sensitizes cisplatin-sensitive and resistant hepatocellular carcinoma cells to cisplatin through apoptotic and autophagic cell death via SCF βTrCP-mediated eEF2K degradation. Oncotarget 7 29050305
2012 Thermal injury activates the eEF2K-dependent eEF2 pathway in pediatric patients. JPEN. Journal of parenteral and enteral nutrition 7 22269896
2024 eEF2K alleviates doxorubicin-induced cardiotoxicity by inhibiting GSK3β and improving autophagy dysfunction. Cell biology and toxicology 6 39708064
2020 Bicuculline regulated protein synthesis is dependent on Homer1 and promotes its interaction with eEF2K through mTORC1-dependent phosphorylation. Journal of neurochemistry 6 32892352
2025 Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans. Nature communications 5 39966347
2022 In silico, synthesis and anticancer evaluation of benzamide tryptamine derivatives as novel eEF2K inhibitors. Bioorganic & medicinal chemistry letters 4 35483594
2023 Regulating eEF2 and eEF2K in skeletal muscle by exercise. Archives of physiology and biochemistry 3 36633938
2022 Ghrelin rapidly elevates protein synthesis in vitro by employing the rpS6K-eEF2K-eEF2 signalling axis. Cellular and molecular life sciences : CMLS 3 35841486
2022 eEF-2K knockdown synergizes with STS treatment to inhibit cell proliferation, migration, and invasion via the TG2/ERK pathway in A549 cells. Journal of biochemical and molecular toxicology 3 35844142
2018 Sustained protein synthesis and reduced eEF2K levels in TAp73-\- mice brain: a possible compensatory mechanism. Cell cycle (Georgetown, Tex.) 3 30507330
2016 Application of Eukaryotic Elongation Factor-2 Kinase (eEF-2K) for Cancer Therapy: Expression, Purification, and High-Throughput Inhibitor Screening. Methods in molecular biology (Clifton, N.J.) 3 26501899
2025 Indole and Coumarin Derivatives Targeting EEF2K in Aβ Folding Reporter Cells. Journal of neurochemistry 2 39754378
2025 In-Silico Screening-Based Discovery of New Natural eEF2K Inhibitors with Neuritogenic Activity. ACS medicinal chemistry letters 2 40104800
2025 Targeting eEF2K induces oxidative stress and sensitizes cancer cells to ferroptosis induction. European journal of pharmacology 2 40409701
2025 Inhibition of eEF-2K Enhances the Antitumor Efficacy of NK Cells. Cancer immunology research 2 40506255
2020 Direct Medial Entorhinal Cortex Input to Hippocampal CA3 Is Crucial for eEF2K Inhibitor-Induced Neuronal Oscillations in the Mouse Hippocampus. Frontiers in cellular neuroscience 2 32210764
2016 Tunable Liaisons: eEF-2K, CaM, and Calcium. Structure (London, England : 1993) 2 27602990
2026 eEF2K promotes immune evasion in melanoma via Cyclin D1-mediated stabilization of PD-L1. Journal of immunology (Baltimore, Md. : 1950) 1 41100192
2025 Discovery of fluorescent theranostic molecular glues for real-time visualization and target degradation toward eEF2K. European journal of medicinal chemistry 1 40997621
2025 Overactive Neuronal eEF2K/eEF2 signaling is associated with cognitive impairment and apathy-like behavior. Molecular psychiatry 1 41392093
2025 Duhuo Jisheng Decoction mitigates postmenopausal rheumatoid arthritis by suppressing eEF2K-mediated cellular senescence. Pharmacological research 1 41429683
2023 Impact of silencing eEF2K expression on the malignant properties of chordoma. Molecular biology reports 1 36652154
2022 [Effects of GSK3β/eEF2K signaling pathway on pulmonary fibrosis in mice]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 1 35634666
2022 A functional eEF2K-eEF2 pathway in the NAc is critical for the expression of cocaine-induced psychomotor sensitisation and conditioned place preference. Translational psychiatry 1 36319619
2021 Discovery of Novel eEF2K Inhibitors Using HTS Fingerprint Generated from Predicted Profiling of Compound-Protein Interactions. Medicines (Basel, Switzerland) 1 34065377
2026 Eukaryotic elongation factor 2 kinase (eEF2K): Mechanisms and pharmacological significance in metabolic diseases. International journal of biological macromolecules 0 41819312
2025 Licochalcone A suppresses pancreatic ductal adenocarcinoma progression by targeting eEF2K-mediated pyroptosis. Frontiers in pharmacology 0 40567376
2025 Pharmacologic targeting of eEF2K in cardiovascular diseases: Mechanisms and potential clinical applications. European journal of pharmacology 0 41109400
2024 eEF-2K Deficiency Boosts the Virus-Specific Effector CD8+ T Cell Responses During Viral Infection. Viruses 0 39861816

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