elongation factor 2 kinase

Summary

Gene Symbol: elongation factor 2 kinase
Description: eukaryotic elongation factor 2 kinase
Alias: HSU93850, eEF-2K, eukaryotic elongation factor 2 kinase, alternative protein EEF2K, calcium/calmodulin-dependent eukaryotic elongation factor-2 kinase, calmodulin-dependent protein kinase III, eEF-2 kinase, elongation factor-2 kinase, eukaroytic elongation factor 2 kinase
Species: human
Products:     elongation factor 2 kinase

Top Publications

  1. Cheng Y, Li H, Ren X, Niu T, Hait W, Yang J. Cytoprotective effect of the elongation factor-2 kinase-mediated autophagy in breast cancer cells subjected to growth factor inhibition. PLoS ONE. 2010;5:e9715 pubmed publisher
  2. Diggle T, Subkhankulova T, Lilley K, Shikotra N, Willis A, Redpath N. Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity. Biochem J. 2001;353:621-6 pubmed
    ..Our data demonstrate an important role for the phosphorylation of Ser-499 in the activation of eEF-2K by PKA and the inhibition of protein synthesis. ..
  3. Smith E, Proud C. cdc2-cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner. EMBO J. 2008;27:1005-16 pubmed publisher
    ..These data closely match the control of Ser359 phosphorylation and indicate that cdc2 may be regulated by mTORC1. ..
  4. Tavares C, O Brien J, Abramczyk O, Devkota A, Shores K, Ferguson S, et al. Calcium/calmodulin stimulates the autophosphorylation of elongation factor 2 kinase on Thr-348 and Ser-500 to regulate its activity and calcium dependence. Biochemistry. 2012;51:2232-45 pubmed publisher
    b>Eukaryotic elongation factor 2 kinase (eEF-2K) is an atypical protein kinase regulated by Ca(2+) and calmodulin (CaM)...
  5. Tekedereli I, Alpay S, Tavares C, Cobanoglu Z, Kaoud T, Sahin I, et al. Targeted silencing of elongation factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer. PLoS ONE. 2012;7:e41171 pubmed publisher
    b>Eukaryotic elongation factor 2 kinase (eEF-2K), through its phosphorylation of elongation factor 2 (eEF2), provides a mechanism by which cells can control the rate of the elongation phase of protein synthesis...
  6. Ashour A, Abdel Aziz A, Mansour A, Alpay S, Huo L, Ozpolat B. Targeting elongation factor-2 kinase (eEF-2K) induces apoptosis in human pancreatic cancer cells. Apoptosis. 2014;19:241-58 pubmed publisher
  7. Nairn A, Palfrey H. Identification of the major Mr 100,000 substrate for calmodulin-dependent protein kinase III in mammalian cells as elongation factor-2. J Biol Chem. 1987;262:17299-303 pubmed
    ..These results suggest that intracellular Ca2+ inhibits protein synthesis in mammalian cells via CaM-dependent protein kinase III-catalyzed phosphorylation of EF-2. ..
  8. Wang X, Li W, Williams M, Terada N, Alessi D, Proud C. Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J. 2001;20:4370-9 pubmed
    b>Elongation factor 2 kinase (eEF2k) phosphorylates and inactivates eEF2...
  9. Pigott C, Mikolajek H, Moore C, Finn S, Phippen C, Werner J, et al. Insights into the regulation of eukaryotic elongation factor 2 kinase and the interplay between its domains. Biochem J. 2012;442:105-18 pubmed publisher
    eEF2K (eukaryotic elongation factor 2 kinase) is a Ca2+/CaM (calmodulin)-dependent protein kinase which regulates the translation elongation machinery...

More Information

Publications132 found, 100 shown here

  1. Ryazanov A, Ward M, Mendola C, Pavur K, Dorovkov M, Wiedmann M, et al. Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase. Proc Natl Acad Sci U S A. 1997;94:4884-9 pubmed
    ..This suggests that eEF-2 kinase and MHCK A are members of a new class of protein kinases with a novel catalytic domain structure. ..
  2. Knebel A, Morrice N, Cohen P. A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. EMBO J. 2001;20:4360-9 pubmed
    ..It was purified and identified as eukaryotic elongation factor 2 kinase (eEF2K). SAPK4/p38delta phosphorylated eEF2K at Ser359 in vitro, causing its inactivation...
  3. Knebel A, Haydon C, Morrice N, Cohen P. Stress-induced regulation of eukaryotic elongation factor 2 kinase by SB 203580-sensitive and -insensitive pathways. Biochem J. 2002;367:525-32 pubmed
    ..Since the phosphorylation of Ser-377 does not inhibit eEF2 kinase in vitro, our results suggest that anisomycin or TNF-alpha inhibit eEF2 kinase via the phosphorylation of Ser-359. ..
  4. Browne G, Proud C. A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin. Mol Cell Biol. 2004;24:2986-97 pubmed
    ..eEF2 kinase is thus a target for mTOR signaling independently of previously known downstream components of the pathway. ..
  5. Arora S, Yang J, Hait W. Identification of the ubiquitin-proteasome pathway in the regulation of the stability of eukaryotic elongation factor-2 kinase. Cancer Res. 2005;65:3806-10 pubmed
  6. Pavur K, Petrov A, Ryazanov A. Mapping the functional domains of elongation factor-2 kinase. Biochemistry. 2000;39:12216-24 pubmed
    ..The amino acid sequence of the carboxyl-terminal domain of eEF-2 kinase displays similarity to several proteins, all of which contain repeats of a 36-amino acid motif that we named "motif 36". ..
  7. Browne G, Finn S, Proud C. Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398. J Biol Chem. 2004;279:12220-31 pubmed
    ..Thus, AMPK and eEF2 kinase may provide a key link between cellular energy status and the inhibition of protein synthesis, a major consumer of metabolic energy. ..
  8. Hait W, Wu H, Jin S, Yang J. Elongation factor-2 kinase: its role in protein synthesis and autophagy. Autophagy. 2006;2:294-6 pubmed
    ..Therefore, eEF-2 kinase activation may be a part of a survival mechanism in glioblastoma, and targeting this kinase may represent a novel approach to cancer treatment. ..
  9. Zhang L, Zhang Y, Liu X, Qin Z, Yang J. Expression of elongation factor-2 kinase contributes to anoikis resistance and invasion of human glioma cells. Acta Pharmacol Sin. 2011;32:361-7 pubmed publisher
    ..eEF-2 kinase expression may serve as a prognostic marker and a novel target for cancer therapy. ..
  10. Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo A, Kool M, et al. The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell. 2013;153:1064-79 pubmed publisher
    Metabolic adaptation is essential for cell survival during nutrient deprivation. We report that eukaryotic elongation factor 2 kinase (eEF2K), which is activated by AMP-kinase (AMPK), confers cell survival under acute nutrient depletion ..
  11. Lu M, Kjellin H, Fotouhi O, Lee L, Nilsson I, Haglund F, et al. Molecular profiles of oxyphilic and chief cell parathyroid adenoma. Mol Cell Endocrinol. 2018;470:84-95 pubmed publisher
    ..Chief and oxyphilic cell parathyroid adenomas have partly overlapping but also distinct molecular profiles. The calmodulin-eEF2K, TR4 and p53 pathways may be involved in the tumor development. ..
  12. Shi N, Chen X, Liu R, Wang D, Su M, Wang Q, et al. Eukaryotic elongation factors 2 promotes tumor cell proliferation and correlates with poor prognosis in ovarian cancer. Tissue Cell. 2018;53:53-60 pubmed publisher
    ..Finally, we hypothesize that eEF2 may be activated in a positive feedback cycle through inactivation of eEF2K via the PI3K/Akt/mTOR pathway. These data provide novel insights into developing experimental therapies for ovarian cancer. ..
  13. Gu H, Chen J, Song Y, Shao H. 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. Cell Physiol Biochem. 2018;51:2136-2147 pubmed publisher
    ..Our findings indicate that GAPLINC promotes NSCLC tumorigenesis by regulating miR-661/eEF2K cascade and provide new insights for the pathogenesis underlying NSCLC and potential targets for therapeutic strategy. ..
  14. Edupuganti R, Wang Q, Tavares C, Chitjian C, Bachman J, Ren P, et al. Synthesis and biological evaluation of pyrido[2,3-d]pyrimidine-2,4-dione derivatives as eEF-2K inhibitors. Bioorg Med Chem. 2014;22:4910-6 pubmed publisher
    ..The results of this work will shed light on the further design and optimization of novel pyrido[2,3-d]pyrimidine analogs as eEF-2K inhibitors. ..
  15. Kameshima S, Kazama K, Okada M, Yamawaki H. Eukaryotic elongation factor 2 kinase mediates monocrotaline-induced pulmonary arterial hypertension via reactive oxygen species-dependent vascular remodeling. Am J Physiol Heart Circ Physiol. 2015;308:H1298-305 pubmed publisher
    ..b>Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca(2+)/calmodulin-dependent protein kinase...
  16. Adaikkan C, Taha E, Barrera I, David O, Rosenblum K. Calcium/Calmodulin-Dependent Protein Kinase II and Eukaryotic Elongation Factor 2 Kinase Pathways Mediate the Antidepressant Action of Ketamine. Biol Psychiatry. 2018;84:65-75 pubmed publisher
    ..We also used eukaryotic elongation factor 2 kinase (eEF2K) (also known as CaMKIII) knockout mice...
  17. Yu P, Wang H, Tian M, Li A, Chen X, Wang X, et al. Eukaryotic elongation factor-2 kinase regulates the cross-talk between autophagy and pyroptosis in doxorubicin-treated human melanoma cells in vitro. Acta Pharmacol Sin. 2019;: pubmed publisher
  18. Jiang S, Guan Y, Chen X, Ge P, Wang X, Lao Y, et al. Tubeimoside-1, a triterpenoid saponin, induces cytoprotective autophagy in human breast cancer cells in vitro via Akt-mediated pathway. Acta Pharmacol Sin. 2018;: pubmed publisher
    ..Our results demonstrate the role and mechanism of TBMS1 in activating autophagy, suggesting that inhibition of cytoprotective autophagy may act as a therapeutic strategy to reinforce the activity of TBMS1 against cancers. ..
  19. Kodama T, Okada M, Yamawaki H. Eukaryotic elongation factor 2 kinase inhibitor, A484954 inhibits noradrenaline-induced acute increase of blood pressure in rats. J Vet Med Sci. 2019;81:35-41 pubmed publisher
    ..In summary, it was concluded that A484954 lowers NA-induced BP rise perhaps through activation of β2-receptor-Kir channel and subsequent vasorelaxation via inhibiting eEF2K activity. ..
  20. Wang N, Feng Y, Tan H, Cheung F, Hong M, Lao L, et al. Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma. J Ethnopharmacol. 2015;164:309-18 pubmed publisher
    ..In nutrient deprived HCC cells with inactivated eEF2, the inhibitory effect of HLJDD in tumor cell expansion was interfered. Our results indicate that HLJDD has potential in blocking HCC progression with involvement of eEF2 inhibition. ..
  21. Faller W, Jackson T, Knight J, Ridgway R, Jamieson T, Karim S, et al. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature. 2015;517:497-500 pubmed publisher
  22. Campbell S, Franks C, Borne A, Shin M, Zhang L, Hsu K. Chemoproteomic Discovery of a Ritanserin-Targeted Kinase Network Mediating Apoptotic Cell Death of Lung Tumor Cells. Mol Pharmacol. 2018;94:1246-1255 pubmed publisher
    ..encephalitis virus-related kinase, rapidly accelerated fibrosarcoma (RAF)] signaling, metabolism [eukaryotic elongation factor 2 kinase, eukaryotic translation initiation factor 2-α kinase 4], and DNA damage response [tousled-..
  23. Zhao Y, Tian Y, Liu L, Zhan J, Hou X, Chen X, et al. Inhibiting eEF-2 kinase-mediated autophagy enhanced the cytocidal effect of AKT inhibitor on human nasopharyngeal carcinoma. Drug Des Devel Ther. 2018;12:2655-2663 pubmed publisher
    ..eEF-2 kinase-mediated autophagy induced by AKT inhibition played a protective role in NPC cells. Inhibition of eEF-2 kinase may be an effective method for increasing the efficacy of an AKT inhibitor such as MK-2206 in NPC. ..
  24. Hizli A, Chi Y, Swanger J, Carter J, Liao Y, Welcker M, et al. Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase. Mol Cell Biol. 2013;33:596-604 pubmed publisher
    ..Because all known eEF2 regulation is exerted via eEF2K, S595 phosphorylation may globally couple the cell cycle machinery to regulatory pathways that impact eEF2K activity. ..
  25. Kenney J, Genheden M, Moon K, Wang X, Foster L, Proud C. Eukaryotic elongation factor 2 kinase regulates the synthesis of microtubule-related proteins in neurons. J Neurochem. 2016;136:276-84 pubmed publisher
    ..Elongation is primarily regulated via eukaryotic elongation factor 2 kinase (eEF2K)...
  26. Russnes H, Caldas C. eEF2K--a new target in breast cancers with combined inactivation of p53 and PTEN. EMBO Mol Med. 2014;6:1512-4 pubmed publisher
    ..The pursuit of druggable targets for each of these subtypes is now pressing. This is elegantly illustrated by the work of Liu et al (2014). ..
  27. Moore C, Wang X, Xie J, Pickford J, Barron J, Regufe da Mota S, et al. Elongation factor 2 kinase promotes cell survival by inhibiting protein synthesis without inducing autophagy. Cell Signal. 2016;28:284-93 pubmed publisher
    b>Eukaryotic elongation factor 2 kinase (eEF2K) inhibits the elongation stage of protein synthesis by phosphorylating its only known substrate, eEF2. eEF2K is tightly regulated by nutrient-sensitive signalling pathways...
  28. Kodama T, Okada M, Yamawaki H. Mechanisms underlying the relaxation by A484954, a eukaryotic elongation factor 2 kinase inhibitor, in rat isolated mesenteric artery. J Pharmacol Sci. 2018;137:86-92 pubmed publisher
    b>Eukaryotic elongation factor 2 kinase (eEF2K) is a calmodulin-related protein kinase which regulates protein translation. A484954 is an inhibitor of eEF2K...
  29. McCamphill P, Farah C, Anadolu M, Hoque S, Sossin W. Bidirectional regulation of eEF2 phosphorylation controls synaptic plasticity by decoding neuronal activity patterns. J Neurosci. 2015;35:4403-17 pubmed publisher
    ..Thus, bidirectional regulation of eEF2 is critical for decoding distinct activity patterns at synapses by activating distinct modes of translation regulation. ..
  30. Yao Z, Li J, Liu Z, Zheng L, Fan N, Zhang Y, et al. Integrative bioinformatics and proteomics-based discovery of an eEF2K inhibitor (cefatrizine) with ER stress modulation in breast cancer cells. Mol Biosyst. 2016;12:729-36 pubmed publisher
  31. Liu L, Huang P, Wang Z, Chen N, Tang C, Lin Z, et al. Inhibition of eEF-2 kinase sensitizes human nasopharyngeal carcinoma cells to lapatinib-induced apoptosis through the Src and Erk pathways. BMC Cancer. 2016;16:813 pubmed
    ..The results of this study suggest that targeting eEF-2 kinase may improve the efficacy of therapeutic interventions such as lapatinib in NPC cells. ..
  32. Gobikrushanth M, Purfield D, Colazo M, Butler S, Wang Z, Ambrose D. The relationship between serum anti-Müllerian hormone concentrations and fertility, and genome-wide associations for anti-Müllerian hormone in Holstein cows. J Dairy Sci. 2018;101:7563-7574 pubmed publisher
  33. Bircan H, Gurbuz N, Pataer A, Caner A, Kahraman N, Bayraktar E, et al. 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. 2018;124:31-39 pubmed publisher
  34. Shahbazi R, Asik E, Kahraman N, Turk M, Ozpolat B, Ulubayram K. Modified gold-based siRNA nanotherapeutics for targeted therapy of triple-negative breast cancer. Nanomedicine (Lond). 2017;12:1961-1973 pubmed publisher
    In this study, we aimed to therapeutically target eukaryotic elongation factor 2 kinase (eEF-2K) in an in vivo triple-negative breast cancer (TNBC) tumor model...
  35. Leprivier G, Sorensen P. How does oncogene transformation render tumor cells hypersensitive to nutrient deprivation?. Bioessays. 2014;36:1082-90 pubmed publisher
    ..emerging mechanism involving the deregulation of mRNA translation elongation through inhibition of eukaryotic elongation factor 2 kinase (eEF2K) is presented...
  36. Leprivier G, Rotblat B, Khan D, Jan E, Sorensen P. Stress-mediated translational control in cancer cells. Biochim Biophys Acta. 2015;1849:845-60 pubmed publisher
    ..This article is part of a Special Issue entitled: Translation and Cancer. ..
  37. Wang F, Qiu Y, Zhang H, Hanson P, Ye X, Zhao G, et al. Heat shock protein 70 promotes coxsackievirus B3 translation initiation and elongation via Akt-mTORC1 pathway depending on activation of p70S6K and Cdc2. Cell Microbiol. 2017;19: pubmed publisher
    ..and cell division cycle protein 2 homolog (Cdc2)-mediated phosphorylation and inactivation of eukaryotic elongation factor 2 kinase. We also determined the position of Cdc2 in this signal pathway, indicating that Cdc2 is regulated ..
  38. Jan A, Jansonius B, Delaidelli A, Bhanshali F, An Y, Ferreira N, et al. Activity of translation regulator eukaryotic elongation factor-2 kinase is increased in Parkinson disease brain and its inhibition reduces alpha synuclein toxicity. Acta Neuropathol Commun. 2018;6:54 pubmed publisher
    ..These data suggest a role for eEF2K activity in AS toxicity, and support eEF2K inhibition as a potential target in reducing AS-induced oxidative stress in PD. ..
  39. Crowell K, Steiner J, Coleman C, Lang C. Decreased Whole-Body Fat Mass Produced by Chronic Alcohol Consumption is Associated with Activation of S6K1-Mediated Protein Synthesis and Increased Autophagy in Epididymal White Adipose Tissue. Alcohol Clin Exp Res. 2016;40:1832-45 pubmed publisher
    ..These results demonstrate that the alcohol-induced decrease in whole-body fat mass resulted in part from activation of autophagy in eWAT as protein synthesis was increased and mediated by the specific increase in the activity of S6K1. ..
  40. Delaidelli A, Negri G, Jan A, Jansonius B, El Naggar A, Lim J, et al. MYCN amplified neuroblastoma requires the mRNA translation regulator eEF2 kinase to adapt to nutrient deprivation. Cell Death Differ. 2017;24:1564-1576 pubmed publisher
    ..We recently identified eukaryotic Elongation Factor 2 Kinase (eEF2K) as a pivotal mediator of the adaptive response of tumor cells to ND...
  41. Argüello R, Reverendo M, Mendes A, Camosseto V, Torres A, Ribas De Pouplana L, et al. SunRiSE - measuring translation elongation at single-cell resolution by means of flow cytometry. J Cell Sci. 2018;131: pubmed publisher
    ..This article has an associated First Person interview with the first author of the paper. ..
  42. Shi Q, Shi J, Luo F, Song G, He X, Xia Y. Major Differences in Hypoxia Tolerance and P38 Regulation Among Different Renal Cells. Cell Physiol Biochem. 2018;46:1483-1492 pubmed publisher
    ..Our data suggest that in response to prolonged hypoxic stress, ERK1/2 and p38 are differentially regulated in three renal cells, while eEF2K is largely down-regulated in all of these cells. ..
  43. Devkota A, Edupuganti R, Yan C, Shi Y, Jose J, Wang Q, et al. Reversible covalent inhibition of eEF-2K by carbonitriles. Chembiochem. 2014;15:2435-42 pubmed publisher
    ..5 Å of the active site Cys146 to form a reversible thioimidate adduct. Because Cys146 is not conserved amongst other related kinases, targeting this residue holds promise for the development of selective covalent inhibitors of eEF-2K. ..
  44. Bayraktar R, Ivan C, Bayraktar E, Kanlikilicer P, Kabil N, Kahraman N, et al. Dual Suppressive Effect of miR-34a on the FOXM1/eEF2-Kinase Axis Regulates Triple-Negative Breast Cancer Growth and Invasion. Clin Cancer Res. 2018;24:4225-4241 pubmed publisher
    ..i>Clin Cancer Res; 24(17); 4225-41. ©2018 AACR. ..
  45. Liong S, Lappas M. Markers of protein synthesis are increased in fetal membranes and myometrium after human labour and delivery. Reprod Fertil Dev. 2018;30:313-329 pubmed publisher
    ..the effect of human labour on the expression of three protein synthesis markers, namely eukaryotic elongation factor 2 kinase (EEF2K), mitogen-activated protein kinase interacting protein kinase 1 (MKNK1) and eukaryotic ..
  46. Zhang P, Riazy M, Gold M, Tsai S, McNagny K, Proud C, et al. Impairing eukaryotic elongation factor 2 kinase activity decreases atherosclerotic plaque formation. Can J Cardiol. 2014;30:1684-8 pubmed publisher
    We tested whether loss of eukaryotic elongation factor 2 kinase (eEF2K) activity in macrophages suppresses development of atherosclerosis by transplanting bone marrow from mice with mutant eEF2K into ldlr(-/-) mice...
  47. Will N, Lee K, Hajredini F, Giles D, Abzalimov R, Clarkson M, et al. Structural Dynamics of the Activation of Elongation Factor 2 Kinase by Ca2+-Calmodulin. J Mol Biol. 2018;430:2802-2821 pubmed publisher
    b>Eukaryotic elongation factor 2 kinase (eEF-2K), the only known calmodulin (CaM)-activated α-kinase, phosphorylates eukaryotic elongation factor 2 (eEF-2) on a specific threonine (Thr-56) diminishing its affinity for the ribosome and ..
  48. Tang X, Wu X, Xu L, Fang Y, Wang P, Zhu G, et al. eEF-2 Phosphorylation Down-Regulates P-Glycoprotein Over-Expression in Rat Brain Microvessel Endothelial Cells. PLoS ONE. 2015;10:e0125389 pubmed publisher
    ..eEF-2K/eEF-2 should have played an important role in the regulation of P-glycoprotein expression in RBMECs. eEF-2K inhibitor NH125 could serve as an efficacious anti-multidrug resistant agent. ..
  49. Zhu H, Song H, Chen G, Yang X, Liu J, Ge Y, et al. eEF2K promotes progression and radioresistance of esophageal squamous cell carcinoma. Radiother Oncol. 2017;124:439-447 pubmed publisher
    ..05). eEF2K induced progression and radioresistance in ESCC, which may be a novel therapeutic target for ESCC to increase radiosensitivity. ..
  50. Chu H, Liao Y, Novak J, Hu Z, Merkin J, Shymkiv Y, et al. Germline quality control: eEF2K stands guard to eliminate defective oocytes. Dev Cell. 2014;28:561-572 pubmed publisher
    ..Here, we demonstrate that elongation factor 2 kinase (eEF2K), an evolutionarily conserved regulator of protein synthesis, functions to maintain germline ..
  51. Qadir F, Aziz M, Sari C, Ma H, Dai H, Wang X, et al. Transcriptome reprogramming by cancer exosomes: identification of novel molecular targets in matrix and immune modulation. Mol Cancer. 2018;17:97 pubmed publisher
    ..Molecular pathways and biomarkers identified in this study may be clinically exploitable for developing novel liquid-biopsy based diagnostics and immunotherapies. ..
  52. Guo Y, Zhao Y, Wang G, Chen Y, Jiang Y, Ouyang L, et al. Design, synthesis and structure-activity relationship of a focused library of ?-phenylalanine derivatives as novel eEF2K inhibitors with apoptosis-inducing mechanisms in breast cancer. Eur J Med Chem. 2018;143:402-418 pubmed publisher
    b>Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca2+/calmudulin-dependent protein kinase, belonging to a small family of an atypical Ser/Thr-protein kinase...
  53. Ma T, Chen Y, Vingtdeux V, Zhao H, Viollet B, Marambaud P, et al. Inhibition of AMP-activated protein kinase signaling alleviates impairments in hippocampal synaptic plasticity induced by amyloid β. J Neurosci. 2014;34:12230-8 pubmed publisher
    ..Our findings describe a previously unrecognized role of aberrant AMPK signaling in AD-related synaptic pathophysiology and reveal a potential therapeutic target for AD. ..
  54. Kenney J, Sorokina O, Genheden M, Sorokin A, Armstrong J, Proud C. Dynamics of elongation factor 2 kinase regulation in cortical neurons in response to synaptic activity. J Neurosci. 2015;35:3034-47 pubmed publisher
    ..in cells, is the elongation phase of mRNA translation, which is controlled by the Ca(2+)/CaM-dependent elongation factor 2 kinase (eEF2K)...
  55. Piper M, Lee A, van Horck F, McNeilly H, Lu T, Harris W, et al. Differential requirement of F-actin and microtubule cytoskeleton in cue-induced local protein synthesis in axonal growth cones. Neural Dev. 2015;10:3 pubmed publisher
    ..of translation initiation, microtubules were required for netrin-1-induced activation of eukaryotic elongation factor 2 kinase (eEF2K) and eEF2...
  56. Zhang H, Wang F, Qiu Y, Ye X, Hanson P, Shen H, et al. Emodin inhibits coxsackievirus B3 replication via multiple signalling cascades leading to suppression of translation. Biochem J. 2016;473:473-85 pubmed publisher
    ..1/2)/p90(RSK) (p90 ribosomal S6 kinase) and Ca(2+)/calmodulin, leading to activation of eEF2K (eukaryotic elongation factor 2 kinase) and subsequent inactivation of eEF2 (eukaryotic elongation factor 2), resulting in inhibition of ..
  57. Gismondi A, Caldarola S, Lisi G, Juli G, Chellini L, Iadevaia V, et al. Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of terminal oligopyrimidine (TOP) mRNAs on polysomes. Nucleic Acids Res. 2014;42:12668-80 pubmed publisher
    ..an additional response to ribosomal stress that includes the activation of eukaryotic translation elongation factor 2 kinase with a consequent inhibition of translation elongation...
  58. Zeng Q, Liu J, Cao P, Li J, Liu X, Fan X, et al. Inhibition of REDD1 Sensitizes Bladder Urothelial Carcinoma to Paclitaxel by Inhibiting Autophagy. Clin Cancer Res. 2018;24:445-459 pubmed publisher
    ..i>Clin Cancer Res; 24(2); 445-59. ©2017 AACR. ..
  59. Kabil N, Bayraktar R, Kahraman N, Mokhlis H, Calin G, Lopez Berestein G, et al. 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 Res Treat. 2018;171:593-605 pubmed publisher
    ..We have previously shown that eukaryotic elongation factor 2 kinase (eEF-2K) is highly expressed in TNBC cells, is associated with poor patient survival and prognosis,..
  60. Shenkman B, Belova S, Lomonosova Y, Kostrominova T, Nemirovskaya T. Calpain-dependent regulation of the skeletal muscle atrophy following unloading. Arch Biochem Biophys. 2015;584:36-41 pubmed publisher
    ..3-fold in HSPD) and eEF2k (1.8-fold in HS vs 0.6-fold in HSPD) mRNA. Our study indicates that blocking of calpain during unloading decreases skeletal muscle atrophy by inhibiting UPP activation and preserving anabolic signaling. ..
  61. McKnight R, Yost C, Zinkhan E, Fu Q, Callaway C, Fung C. Intrauterine growth restriction inhibits expression of eukaryotic elongation factor 2 kinase, a regulator of protein translation. Physiol Genomics. 2016;48:616-25 pubmed publisher
    ..Transcriptional upregulation and activation of eukaryotic elongation factor 2 kinase (eEF2K) blocks peptide elongation by phosphorylating eukaryotic elongation factor 2...
  62. Xu B, Zhang Y, Du X, Li J, Zi H, Bu J, et al. Neurons secrete miR-132-containing exosomes to regulate brain vascular integrity. Cell Res. 2017;27:882-897 pubmed publisher
    ..endothelial cadherin (VE-cadherin), an important adherens junction protein, by directly targeting eukaryotic elongation factor 2 kinase (eef2k)...
  63. Meyers J, Salling M, Almli L, Ratanatharathorn A, Uddin M, Galea S, et al. Frequency of alcohol consumption in humans; the role of metabotropic glutamate receptors and downstream signaling pathways. Transl Psychiatry. 2015;5:e586 pubmed publisher
    ..In conclusion, insights from rodent studies enabled the identification of novel human alcohol candidate genes within the mGluR-eEF2-AMPAR pathway. ..
  64. Heise C, Taha E, Murru L, Ponzoni L, Cattaneo A, Guarnieri F, et al. eEF2K/eEF2 Pathway Controls the Excitation/Inhibition Balance and Susceptibility to Epileptic Seizures. Cereb Cortex. 2017;27:2226-2248 pubmed publisher
    ..b>Eukaryotic elongation factor 2 kinase (eEF2K) is a highly regulated, ubiquitous kinase involved in the control of protein translation...
  65. Gurbuz N, Asoglu M, Ashour A, Salama S, Kilic G, Ozpolat B. A selective serotonin 5-HT1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells. Eur J Obstet Gynecol Reprod Biol. 2016;206:114-119 pubmed publisher
    ..muscle actin (?-SMA) expressions and the activity of Mitogen Activated Protein Kinase (MAPK) ERK and Elongation Factor 2 kinase (EF2K) pathways...
  66. Crawford D, Ramirez D, Trauterman B, Monteggia L, Kavalali E. Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy. Nat Commun. 2017;8:14436 pubmed publisher
    ..high-frequency glutamate release and augments unitary event amplitudes by reducing postsynaptic eukaryotic elongation factor 2 kinase (eEF2K) activity subsequent to the reduction in N-methyl-D-aspartate receptor (NMDAR) activity...
  67. McCamphill P, Ferguson L, Sossin W. A decrease in eukaryotic elongation factor 2 phosphorylation is required for local translation of sensorin and long-term facilitation in Aplysia. J Neurochem. 2017;142:246-259 pubmed publisher
    ..These results identify decreases in eEF2 phosphorylation as a critical downstream effector of mTOR required for long-term plasticity and identify an important translational target regulated by decreases in eEF2 phosphorylation. ..
  68. Bayraktar R, Pichler M, Kanlikilicer P, Ivan C, Bayraktar E, Kahraman N, et al. MicroRNA 603 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting elongation factor 2 kinase. Oncotarget. 2017;8:11641-11658 pubmed publisher
    ..The lack of effective targeted therapies for TNBC represents an unmet therapeutic challenge. Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical calcium/calmodulin-dependent serine/threonine kinase that promotes TNBC ..
  69. Ramirez D, Crawford D, Chanaday N, Trauterman B, Monteggia L, Kavalali E. Loss of Doc2-Dependent Spontaneous Neurotransmission Augments Glutamatergic Synaptic Strength. J Neurosci. 2017;37:6224-6230 pubmed publisher
    ..with reduced phosphorylation levels of eukaryotic elongation factor 2 and also requires the presence of elongation factor 2 kinase. Together, these data suggest that spontaneous neurotransmission independently contributes to the ..
  70. Pan Z, Chen Y, Liu J, Jiang Q, Yang S, Guo L, et al. 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. Eur J Med Chem. 2018;144:517-528 pubmed publisher
    ..Our results suggested that these novel PLK1/EEF2K dual inhibitors can be used as lead compounds for further development breast cancer chemotherapy. ..
  71. Wang Y, Huang G, Wang Z, Qin H, Mo B, Wang C. Elongation factor-2 kinase acts downstream of p38 MAPK to regulate proliferation, apoptosis and autophagy in human lung fibroblasts. Exp Cell Res. 2018;363:291-298 pubmed publisher
  72. Tavares C, Devkota A, Dalby K, Cho E. Application of Eukaryotic Elongation Factor-2 Kinase (eEF-2K) for Cancer Therapy: Expression, Purification, and High-Throughput Inhibitor Screening. Methods Mol Biol. 2016;1360:19-33 pubmed publisher
    ..Here, we describe the purification of the protein kinase, eEF-2K, and the utilization of three biochemical assays in the course of identifying small molecules that block its enzymatic reaction. ..
  73. Wang G, Qi X, Li J. [Eukaryotic elongation factor 2 kinase and cancer]. Yao Xue Xue Bao. 2015;50:808-13 pubmed
    b>Eukaryotic elongation factor 2 kinase (eEF2K) is well known as a Ca2+/calmodulin (CaM)-dependent kinase...
  74. Kameshima S, Okada M, Yamawaki H. Expression and localization of calmodulin-related proteins in brain, heart and kidney from spontaneously hypertensive rats. Biochem Biophys Res Commun. 2016;469:654-8 pubmed publisher
    ..We have previously demonstrated that expression level of calmodulin-related proteins including eukaryotic elongation factor 2 kinase (eEF2K), death-associated protein kinase (DAPK)3, and histone deacetylase (HDAC)4 was specifically ..
  75. de Gassart A, Demaria O, Panes R, Zaffalon L, Ryazanov A, Gilliet M, et al. Pharmacological eEF2K activation promotes cell death and inhibits cancer progression. EMBO Rep. 2016;17:1471-1484 pubmed
    Activation of the elongation factor 2 kinase (eEF2K) leads to the phosphorylation and inhibition of the elongation factor eEF2, reducing mRNA translation rates...
  76. Weng W, Chen Y, Wang M, Zhuang Y, Behnisch T. Potentiation of Schaffer-Collateral CA1 Synaptic Transmission by eEF2K and p38 MAPK Mediated Mechanisms. Front Cell Neurosci. 2016;10:247 pubmed
    The elongation factor 2 kinase (eEF2K), likewise known as CaMKIII, has been demonstrated to be involved in antidepressant responses of NMDA receptor antagonists...
  77. Ji C, Xu Q, Guo L, Wang X, Ren Y, Zhang H, et al. eEF-2 Kinase-targeted miR-449b confers radiation sensitivity to cancer cells. Cancer Lett. 2018;418:64-74 pubmed publisher
    ..These results indicate that miR-449 b, which is frequently down-regulated in radio-resistant cancers, may represent a new critical determinant of radio-sensitivity. ..
  78. Xu Z, Zhao L, Yang X, Ma S, Ge Y, Liu Y, et al. Mmu-miR-125b overexpression suppresses NO production in activated macrophages by targeting eEF2K and CCNA2. BMC Cancer. 2016;16:252 pubmed publisher
    ..These data suggest that mmu-miR-125b decreases NO production in activated macrophages at least partially by suppressing eEF2K and CCNA2 expression. ..
  79. Abelaira H, Réus G, Ignácio Z, Dos Santos M, de Moura A, Matos D, et al. Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex. J Psychiatr Res. 2017;87:81-87 pubmed publisher
    ..p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1)..
  80. Wang L, Hou Y, Yin X, Su J, Zhao Z, Ye X, et al. Rottlerin inhibits cell growth and invasion via down-regulation of Cdc20 in glioma cells. Oncotarget. 2016;7:69770-69782 pubmed publisher
    ..Therefore, down-regulation of Cdc20 by rottlerin could be a promising therapeutic strategy for the treatment of glioma. ..
  81. Song J, Finnerty C, Herndon D, Kraft R, Boehning D, Brooks N, et al. Thermal injury activates the eEF2K-dependent eEF2 pathway in pediatric patients. JPEN J Parenter Enteral Nutr. 2012;36:596-602 pubmed publisher
    ..Total amounts of eEF2 and eEF2K were not altered. Burn induces prolonged activation of eEF2K and eEF2. Alterations in these mediators may contribute to profound hypermetabolism in severely burned patients. ..
  82. Liu X, Zhang L, Zhang Y, Yang J. Roles of eEF-2 kinase in cancer. Chin Med J (Engl). 2012;125:2908-13 pubmed
    ..eEF-2 kinase fills critical niches in the life of a cancer cell and the eEF-2/eEF-2 kinase pathway is a key biochemical sensor. ..
  83. Jan A, Jansonius B, Delaidelli A, Somasekharan S, Bhanshali F, Vandal M, et al. eEF2K inhibition blocks Aβ42 neurotoxicity by promoting an NRF2 antioxidant response. Acta Neuropathol. 2017;133:101-119 pubmed publisher
    ..elegans expressing human Aβ42 in neurons. Taken together, these findings highlight the potential utility of eEF2K inhibition to reduce Aβ-mediated oxidative stress in AD. ..
  84. Deng Z, Luo P, Lai W, Song T, Peng J, Wei H. Myostatin inhibits eEF2K-eEF2 by regulating AMPK to suppress protein synthesis. Biochem Biophys Res Commun. 2017;494:278-284 pubmed publisher
    ..It provided a new mechanism for myostatin regulating protein synthesis and treating muscle atrophy...
  85. Liu J, Voisin V, Wang S, Wang D, Jones R, Datti A, et al. Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K. EMBO Mol Med. 2014;6:1542-60 pubmed publisher
    ..Our results identify a prognostic signature for claudin-low patients and provide a rationale for using eEF2K inhibitors for treatment of TNBC with elevated AKT signaling. ..
  86. Usui T, Okada M, Hara Y, Yamawaki H. Eukaryotic elongation factor 2 kinase regulates the development of hypertension through oxidative stress-dependent vascular inflammation. Am J Physiol Heart Circ Physiol. 2013;305:H756-68 pubmed publisher
    b>Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca2+/calmodulin-dependent protein kinase. We recently demonstrated that eEF2K protein increases in mesenteric artery from spontaneously hypertensive rats (SHR)...
  87. Cheng Y, Ren X, Yuan Y, Shan Y, Li L, Chen X, et al. eEF-2 kinase is a critical regulator of Warburg effect through controlling PP2A-A synthesis. Oncogene. 2016;35:6293-6308 pubmed publisher
    ..These results, which uncover a role of the eEF-2K-mediated control of PP2A-A in tumor cell glycolysis, provide new insights into the regulation of the Warburg effect. ..
  88. Li X, Alafuzoff I, Soininen H, Winblad B, Pei J. Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain. FEBS J. 2005;272:4211-20 pubmed
  89. Ayada K, Yokota K, Kawahara Y, Yamamoto Y, Hirai K, Inaba T, et al. Immune reactions against elongation factor 2 kinase: specific pathogenesis of gastric ulcer from Helicobacter pylori infection. Clin Dev Immunol. 2009;2009:850623 pubmed publisher
    ..This antigen was over-expressed by a stressful (heat-stressed) environment, and was identified as elongation factor 2 kinase (EF-2K) by western blotting. The GU patients' lymphocytes stimulated by H...
  90. Lee K, Alphonse S, Piserchio A, Tavares C, Giles D, Wellmann R, et al. Structural Basis for the Recognition of Eukaryotic Elongation Factor 2 Kinase by Calmodulin. Structure. 2016;24:1441-51 pubmed publisher
    Binding of Ca(2+)-loaded calmodulin (CaM) activates eukaryotic elongation factor 2 kinase (eEF-2K) that phosphorylates eEF-2, its only known cellular target, leading to a decrease in global protein synthesis...
  91. Veglia G, Li G. Tunable Liaisons: eEF-2K, CaM, and Calcium. Structure. 2016;24:1438-9 pubmed publisher
    ..2016) perform NMR analysis of calmodulin (CaM) binding to the eukaryotic elongation factor 2 kinase (eEF-2K)...
  92. Arora S, Yang J, Craft J, Hait W. Detection of anti-elongation factor 2 kinase (calmodulin-dependent protein kinase III) antibodies in patients with systemic lupus erythematosus. Biochem Biophys Res Commun. 2002;293:1073-6 pubmed
    b>Elongation factor 2 kinase (eEF-2K), also known as calmodulin-dependent protein kinase III, is a member of the calmodulin-mediated signaling pathway that links activation of cell surface receptors to cell division...