Phosphorylation of Elongation Factor 2

Ryazanov, Alexey G.; Spirin, Alexander S.

doi:10.1007/978-1-4615-2894-4_21

Cited by 15 publications

(12 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro, eEF2 phosphorylation halts ribosomal translocation until eEF2 is dephosphorylated. Additionally, in the eukaryotic cells types studied to date, eEF2 phosphorylation is associated with reduced protein synthesis (10,11). Phosphorylation of eEF2 is catalyzed by a single protein kinase, eEF2 kinase, whose activity is calcium-and calmodulin-dependent.…”

Section: Activation Of N-methyl-d-aspartate Receptors (Nmdars) Hasmentioning

confidence: 99%

“…Unlike many other calcium-and calmodulin-dependent kinases, eEF2 kinase phosphorylates a single substrate, eEF2 (12). Phosphorylation of eEF2 in other systems, such as during the cell cycle, precedes dramatic shifts in protein expression (11). Other links between protein synthesis inhibition and altered protein expression have been demonstrated (13).…”

Section: Activation Of N-methyl-d-aspartate Receptors (Nmdars) Hasmentioning

confidence: 99%

See 1 more Smart Citation

N -methyl- d -aspartate receptor activation and visual activity induce elongation factor-2 phosphorylation in amphibian tecta: A role for N -methyl- d -aspartate receptors in controlling protein synthesis

Scheetz

Nairn

Constantine‐Paton

1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

N -methyl- d -aspartate receptor (NMDAR) activation has been implicated in forms of synaptic plasticity involving long-term changes in neuronal structure, function, or protein expression. Transcriptional alterations have been correlated with NMDAR-mediated synaptic plasticity, but the problem of rapidly targeting new proteins to particular synapses is unsolved. One potential solution is synapse-specific protein translation, which is suggested by dendritic localization of numerous transcripts and subsynaptic polyribosomes. We report here a mechanism by which NMDAR activation at synapses may control this protein synthetic machinery. In intact tadpole tecta, NMDAR activation leads to phosphorylation of a subset of proteins, one of which we now identify as the eukaryotic translation elongation factor 2 (eEF2). Phosphorylation of eEF2 halts protein synthesis and may prepare cells to translate a new set of mRNAs. We show that NMDAR activation-induced eEF2 phosphorylation is widespread in tadpole tecta. In contrast, in adult tecta, where synaptic plasticity is reduced, this phosphorylation is restricted to short dendritic regions that process binocular information. Biochemical and anatomical evidence shows that this NMDAR activation-induced eEF2 phosphorylation is localized to subsynaptic sites. Moreover, eEF2 phosphorylation is induced by visual stimulation, and NMDAR blockade before stimulation eliminates this effect. Thus, NMDAR activation, which is known to mediate synaptic changes in the developing frog, could produce local postsynaptic alterations in protein synthesis by inducing eEF2 phosphorylation.

show abstract

Section: Activation Of N-methyl-d-aspartate Receptors (Nmdars) Hasmentioning

confidence: 99%

Section: Activation Of N-methyl-d-aspartate Receptors (Nmdars) Hasmentioning

confidence: 99%

N -methyl- d -aspartate receptor activation and visual activity induce elongation factor-2 phosphorylation in amphibian tecta: A role for N -methyl- d -aspartate receptors in controlling protein synthesis

Scheetz

Nairn

Constantine‐Paton

1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…There are two examples of such inhibition (in PC-12 cells [34] and in Xenopus laevis oocytes [35]), that are presumably important for regulation of differentiation and cell development [36]. In this respect, we have examined the phosphorylation of EF-2 in cytoplasmic extracts from differentiated organs of wheat: leaves, roots, normal and etiolated seedlings, pollen, as well as extracts from other plants including leaves and pollen of tobacco, embryos, shoots and roots of corn and pea.…”

mentioning

confidence: 99%

Study of phosphorylation of translation elongation factor 2 (EF‐2) from wheat germ

1993

View full text Add to dashboard Cite

Phosphorylation of elongation factor 2 (EF-2) by specific Ca2?calmodulin-dependent kinase is considered as a possible mechanism of regulation of protein biosynthesis in animal cells at the level of polypeptide chain elongation. In this report we show that wheat germ EF-2 can be intensively phosphorylated by the rabbit reticulocyte EF-2 kinase. Phosphorylation results in inhibition of the activity of plant EF-2 in poly(U)-dependent cell-free translation system. Thus, the activity of EF-2 in plant cells can be potentially regulated by phosphorylation. However, we could not detect endogenous EF-2 kinase activity in wheat germ either in vitro or in vivo. Furthermore, EF-2 kinase activity is not displayed in different organs of wheat and other higher plants.

show abstract

“…1 of Vega et al (37), which shows a gel of [ 32 P]proteins phosphorylated in the presence and absence of prothymosin ␣, all of the bands became more intense in the presence of prothymosin ␣, a result most consistent with a nonspecific effect. Furthermore, it is important to point out that eEF-2 is an abundant protein and that it is rapidly phosphorylated (39). Therefore, in short incubations with labeled ATP it is the most prominent labeled product.…”

Section: Discussionmentioning

confidence: 99%

“…In the presence of Ca 2ϩ , a band at ϳ100 kDa, which can be identified as eEF-2, acquires label rapidly and dominates the electrophoretic pattern (39). Accordingly, we examined the ability of sonicated lysates of NIH3T3 cells to phosphorylate a ϳ100-kDa protein in a series of incubations extending from 1 to 20 min.…”

Section: Phosphorylation Of Sonicated Extracts-cytoplasmic Extracts Fmentioning

confidence: 99%

Does Prothymosin α Affect the Phosphorylation of Elongation Factor 2?

Enkemann

Pavur

Ryazanov

et al. 1999

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Prothymosin ␣ is a small, acidic, essential nuclear protein that plays a poorly defined role in the proliferation and survival of mammalian cells. Recently, Vega et al. proposed that exogenous prothymosin ␣ can specifically increase the phosphorylation of eukaryotic elongation factor 2 (eEF-2) in extracts of NIH3T3 cells (Vega, F. V., Vidal, A., Hellman, U., Wernstedt, C., and Domínguez, F. (1998) J. Biol. Chem. 273, 10147-10152). Using similar lysates prepared by four methods (detergent lysis, Dounce homogenization, digitonin permeabilization, and sonication) and three preparations of prothymosin ␣, one of which was purified by gentle means (the native protein, and a histidine-tagged recombinant prothymosin ␣ expressed either in bacteria or in COS cells), we failed to find a response. A reconstituted system composed of eEF-2, recombinant eEF-2 kinase, calmodulin, and calcium was also unaffected by prothymosin ␣. However, unlike our optimized buffer, Vega's system included a phosphatase inhibitor, 50 mM fluoride, which when evaluated in our laboratories severely reduced phosphorylation of all species. Under these conditions, any procedure that decreases the effective fluoride concentration will relieve the inhibition and appear to activate. Our data do not support a direct relationship between the function of prothymosin ␣ and the phosphorylation of eEF-2.The detailed function of prothymosin ␣ remains cryptic and controversial. The protein is not, as its name intimates, a precursor for much smaller, processed, thymic hormones (1-5). Rather, prothymosin ␣ is exclusively mammalian (see Refs. 6 and 7, and references therein), extremely abundant (8, 9), probably unfolded (10), and highly acidic throughout its length of 109 -110 amino acids (1,11,12). It localizes to the nucleus in intact form in all tissues (13-15). An overview of the prothymosin ␣ literature strongly suggests that the protein plays an essential, but nevertheless undefined, role in the growth and survival of virtually all cells (1, 16 -19). Several laboratories have noted (i) that an increase of greater than 10-fold in the mRNA and the protein occurs when quiescent cells proliferate, (ii) that the amount of prothymosin ␣ in a tissue mirrors its inherent growth rate, and (iii) that prothymosin ␣ is expressed in a chronologically contemporaneous manner with other growth related molecules such as Myc, histone H3, and proliferating cell nuclear antigen (1, 3, 8, 20 -24). However, the most compelling evidence comes from synchronized human myeloma cells, which, when exposed to antisense oligodeoxyribonucleotides directed toward prothymosin ␣ mRNA at several locations, undergo growth arrest (25).The particulars of prothymosin ␣'s function are contested. The amino acid sequence, which should provide clues, is essentially unique. Except for a "classical" bipartite nuclear localization signal included in many otherwise unrelated nuclear proteins, the only shared featured is a reiterated region of glutamic acid residues found also in the Xenopus chromatin remo...

show abstract

Phosphorylation of Elongation Factor 2

Cited by 15 publications

References 117 publications

N -methyl- d -aspartate receptor activation and visual activity induce elongation factor-2 phosphorylation in amphibian tecta: A role for N -methyl- d -aspartate receptors in controlling protein synthesis

N -methyl- d -aspartate receptor activation and visual activity induce elongation factor-2 phosphorylation in amphibian tecta: A role for N -methyl- d -aspartate receptors in controlling protein synthesis

Study of phosphorylation of translation elongation factor 2 (EF‐2) from wheat germ

Does Prothymosin α Affect the Phosphorylation of Elongation Factor 2?

Contact Info

Product

Resources

About