ArticleBiochemistry2012
Calcium/calmodulin stimulates the autophosphorylation of elongation factor 2 kinase on Thr-348 and Ser-500 to regulate its activity and calcium dependence.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- Phosphorylation of a conserved aspartate in the catalytic site of eukaryotic elongation factor 2 kinase.Protein science : a publication of the Protein Society · 2026Article
- Spaceflight alters protein levels and gene expression associated with stress response and metabolic characteristics in human cardiac spheroids.Biomaterials · 2025Article
- Revealing eEF-2 kinase: recent structural insights into function.Trends in biochemical sciences · 2024Review
- Roles of eukaryotic elongation factor 2 kinase (eEF2K) in neuronal plasticity, cognition, and Alzheimer disease.Journal of neurochemistry · 2023Review
- Structure of the complex between calmodulin and a functional construct of eukaryotic elongation factor 2 kinase bound to an ATP-competitive inhibitor.The Journal of biological chemistry · 2023Article
- ADP enhances the allosteric activation of eukaryotic elongation factor 2 kinase by calmodulin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- eEF2K Inhibitor Design: The Progression of Exemplary Structure-Based Drug Design.Molecules (Basel, Switzerland) · 2023Review
- Structural basis for the calmodulin-mediated activation of eukaryotic elongation factor 2 kinase.Science advances · 2022Article
- Discovery of Novel eEF2K Inhibitors Using HTS Fingerprint Generated from Predicted Profiling of Compound-Protein Interactions.Medicines (Basel, Switzerland) · 2021Article
- Target-Driven Design of a Coumarinyl Chalcone Scaffold Based Novel EF2 Kinase Inhibitor Suppresses Breast Cancer GrowthACS pharmacology & translational science · 2021Article
- Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase.Frontiers in molecular biosciences · 2021Review
- Dynamic remodelling of the human host cell proteome and phosphoproteome upon enterovirus infection.Nature communications · 2020Article
- Eukaryotic elongation factor-2 kinase (eEF2K) signaling in tumor and microenvironment as a novel molecular target.Journal of molecular medicine (Berlin, Germany) · 2020Review
- The role of calcium in the interaction between calmodulin and a minimal functional construct of eukaryotic elongation factor 2 kinase.Protein science : a publication of the Protein Society · 2019Article
- Solution Structure of the Carboxy-Terminal Tandem Repeat Domain of Eukaryotic Elongation Factor 2 Kinase and Its Role in Substrate Recognition.Journal of molecular biology · 2019Article
- Structural Dynamics of the Activation of Elongation Factor 2 Kinase by CaJournal of molecular biology · 2018Article
- MicroRNA 603 acts as a tumor suppressor and inhibits triple-negative breast cancer tumorigenesis by targeting elongation factor 2 kinase.Oncotarget · 2017Article
- Signal Integration at Elongation Factor 2 Kinase: THE ROLES OF CALCIUM, CALMODULIN, AND SER-500 PHOSPHORYLATION.The Journal of biological chemistry · 2017Article
- Discovery of new substrates of the elongation factor-2 kinase suggests a broader role in the cellular nutrient response.Cellular signalling · 2017Article
- Structure of the C-Terminal Helical Repeat Domain of Eukaryotic Elongation Factor 2 Kinase.Biochemistry · 2016Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Eukaryotic elongation factor 2 kinase (eEF-2K) is an atypical protein kinase regulated by Ca(2+) and calmodulin (CaM). Its only known substrate is eukaryotic elongation factor 2 (eEF-2), whose phosphorylation by eEF-2K impedes global protein synthesis. To date, the mechanism of eEF-2K autophosphorylation has not been fully elucidated. To investigate the mechanism of autophosphorylation, human eEF-2K was coexpressed with λ-phosphatase and purified from bacteria in a three-step protocol using a CaM affinity column. Purified eEF-2K was induced to autophosphorylate by incubation with Ca(2+)/CaM in the presence of MgATP. Analyzing tryptic or chymotryptic peptides by mass spectrometry monitored the autophosphorylation over 0-180 min. The following five major autophosphorylation sites were identified: Thr-348, Thr-353, Ser-445, Ser-474, and Ser-500. In the presence of Ca(2+)/CaM, robust phosphorylation of Thr-348 occurs within seconds of addition of MgATP. Mutagenesis studies suggest that phosphorylation of Thr-348 is required for substrate (eEF-2 or a peptide substrate) phosphorylation, but not self-phosphorylation. Phosphorylation of Ser-500 lags behind the phosphorylation of Thr-348 and is associated with the Ca(2+)-independent activity of eEF-2K. Mutation of Ser-500 to Asp, but not Ala, renders eEF-2K Ca(2+)-independent. Surprisingly, this Ca(2+)-independent activity requires the presence of CaM.
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