scholarly journals Post-Meal Responses of Elongation Factor 2 (eEF2) and Adenosine Monophosphate-Activated Protein Kinase (AMPK) to Leucine and Carbohydrate Supplements for Regulating Protein Synthesis Duration and Energy Homeostasis in Rat Skeletal Muscle

Nutrients ◽  
2012 ◽  
Vol 4 (11) ◽  
pp. 1723-1739 ◽  
Author(s):  
Gabriel Wilson ◽  
Christopher Moulton ◽  
Peter Garlick ◽  
Tracy Anthony ◽  
Donald Layman
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Protein Kinase ◽  
Energy Homeostasis ◽  
Elongation Factor ◽  
Adenosine Monophosphate ◽  
Rat Skeletal Muscle ◽  
Elongation Factor 2 ◽  
Synthesis Duration

scholarly journals Insights Into the Pathologic Roles and Regulation of Eukaryotic Elongation Factor-2 Kinase

2021 ◽  
Vol 8 ◽  
Author(s):  
Darby J. Ballard ◽  
Hao-Yun Peng ◽  
Jugal Kishore Das ◽  
Anil Kumar ◽  
Liqing Wang ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Elongation Factor ◽  
Protein Translation ◽  
Negative Regulator ◽  
Translation Elongation ◽  
Elongation Factor 2 ◽  
Global Rate ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor

Eukaryotic Elongation Factor-2 Kinase (eEF2K) acts as a negative regulator of protein synthesis, translation, and cell growth. As a structurally unique member of the alpha-kinase family, eEF2K is essential to cell survival under stressful conditions, as it contributes to both cell viability and proliferation. Known as the modulator of the global rate of protein translation, eEF2K inhibits eEF2 (eukaryotic Elongation Factor 2) and decreases translation elongation when active. eEF2K is regulated by various mechanisms, including phosphorylation through residues and autophosphorylation. Specifically, this protein kinase is downregulated through the phosphorylation of multiple sites via mTOR signaling and upregulated via the AMPK pathway. eEF2K plays important roles in numerous biological systems, including neurology, cardiology, myology, and immunology. This review provides further insights into the current roles of eEF2K and its potential to be explored as a therapeutic target for drug development.

Eukaryotic elongation factor-2 (eEF-2) activity in bovine mammary tissue in relation to milk protein synthesis

2002 ◽  
Vol 69 (2) ◽  
pp. 205-212 ◽  
Author(s):  
CLAUS T. CHRISTOPHERSEN ◽  
JAKOB KARLSEN ◽  
METTE O. NIELSEN ◽  
BENT RIIS
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Mammary Gland ◽  
Diphtheria Toxin ◽  
Milk Protein ◽  
Elongation Factor ◽  
Mammary Tissue ◽  
Limiting Factor ◽  
Elongation Factor 2 ◽  
High Level

The amount of protein synthesis translational elongation factor 2 (eEF-2) was estimated employing diphtheria toxin-dependent ADP-ribosylation in samples prepared from small amounts of tissue from mammary gland, skeletal muscle and liver from lactating dairy cows. A very high level of ADP-ribosylatable eEF-2 was found in mammary gland, amounting to 20-times the level found in liver and 50-times the level found in skeletal muscle. This obviously reflects the high protein synthesis activity in mammary tissue. To our knowledge, similar high activities have previously been reported only for cancer cells. A close linear relationship was found between the amount of diphtheria-toxin catalysed ADP-ribosylated eEF-2 and protein and casein output in milk from cows in late lactation. This strongly suggests that eEF-2 may be a limiting factor in milk protein synthesis.

scholarly journals Activation of AMP-Activated Protein Kinase Leads to the Phosphorylation of Elongation Factor 2 and an Inhibition of Protein Synthesis

2002 ◽  
Vol 12 (16) ◽  
pp. 1419-1423 ◽  
Author(s):  
Sandrine Horman ◽  
Gareth J. Browne ◽  
Ulrike Krause ◽  
Jigna V. Patel ◽  
Didier Vertommen ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Elongation Factor ◽  
Elongation Factor 2 ◽  
Inhibition Of Protein Synthesis ◽  
Amp Activated Protein Kinase

scholarly journals Concentration of elongation factor 2 in rat skeletal muscle during protein depletion and re-feeding (Short Communication)

1974 ◽  
Vol 142 (1) ◽  
pp. 185-188 ◽  
Author(s):  
Sunney D. Alexis ◽  
Vernon R. Young ◽  
D. Michael Gill
Keyword(s):  
Skeletal Muscle ◽  
Dietary Protein ◽  
Short Communication ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Elongation Factor ◽  
Rat Skeletal Muscle ◽  
Elongation Factor 2 ◽  
Whole Muscle

Rat skeletal-muscle elongation factor 2 was assayed by causing it to react with NAD+ by using fragment A of diphtheria toxin as the catalyst. Dietary protein restriction decreased the concentration of elongation factor 2 in homogenates of whole muscle. These decreases paralleled a decline in muscle RNA so that the number of molecules of elongation factor 2 per ribosome appeared to be independent of the diet. We conclude that elongation factor 2 is probably not the factor limiting the rate of muscle protein synthesis and is not responsible for the fall in the protein-synthetic rate in vivo observed in the muscles of animals whose dietary protein intake is inadequate.

Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity

2001 ◽  
Vol 353 (3) ◽  
pp. 621-626 ◽  
Author(s):  
Tricia A. DIGGLE ◽  
Tatiana SUBKHANKULOVA ◽  
Kathryn S. LILLEY ◽  
Nita SHIKOTRA ◽  
Anne E. WILLIS ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Elongation Factor ◽  
Luciferase Expression ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Elongation Factor 2 ◽  
Fold Reduction ◽  
Dependent Protein

Elongation factor-2 kinase (eEF-2K) negatively regulates mRNA translation via the phosphorylation and inactivation of elongation factor-2 (eEF-2). We have shown previously that purified eEF-2K can be phosphorylated in vitro by cAMP-dependent protein kinase (PKA) and that this induces significant Ca2+/calmodulin (CaM)-independent eEF-2K activity [Redpath and Proud (1993) Biochem. J. 293, 31–34]. Furthermore, elevation of cAMP levels in adipocytes also increases the level of Ca2+/CaM-independent eEF-2K activity to a similar extent, providing a mechanistic link between elevated cAMP and the inhibition of protein synthesis [Diggle, Redpath, Heesom and Denton (1998) Biochem. J. 336, 525–529]. Here we describe the expression of glutathione S-transferase (GST)-eEF-2K fusion protein and the identification of two serine residues that are phosphorylated by PKA in vitro. Endoproteinase Arg-C digestion of GST-eEF-2K produced two phosphopeptides that were separated by HPLC and sequenced. 32P Radioactivity release from these peptides indicated that the sites of phosphorylation were Ser-365 and Ser-499, both of which lie C-terminal to the catalytic domain. Mutation of these sites to non-phosphorylatable residues indicated that both sites need to be phosphorylated to induce Ca2+/CaM-independent eEF-2K activity in vitro. However, expression of Myc-tagged eEF-2K in HEK 293 cells, followed by treatment with chlorophenylthio-cAMP (CPT-cAMP), showed that Ser-499 phosphorylation alone induced Ca2+/CaM-independent eEF-2K activity in cells. Co-expression of wild-type eEF-2K with luciferase resulted in a 2–3-fold reduction in luciferase expression. Expression of eEF-2K S499D resulted in a 10-fold reduction in luciferase expression despite the fact that this mutant was expressed at very low levels. This indicates that eEF-2K S499D is constitutively active when expressed in cells, thus leading to the suppression of its own expression. 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.

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