Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A high Mr complex isolated from rabbit reticulocytes contains valyl-tRNA synthetase and the four subunits of elongation factor 1 (EF-1). Previously, valyl-tRNA synthetase and the alpha, beta, and delta subunits of EF-1 were shown to be phosphorylated in reticulocytes in response to phorbol 12-myristate 13-acetate (PMA). Phosphorylation of the complex was accompanied by an increase in both valyl-tRNA synthetase and EF-1 activity (Venema, R. C., Peters, H. I., and Traugh, J. A. (1991) J. Biol. Chem., 266, 11993-11998). To investigate phosphorylation of the valyl-tRNA synthetase EF-1 complex in vitro by protein kinase C, the complex has been purified to apparent homogeneity from rabbit reticulocytes by gel filtration on Bio-Gel A-5m, affinity chromatography on tRNA-Sepharose, and fast protein liquid chromatography on Mono Q. Valyl-tRNA synthetase and the beta and delta subunits of EF-1 in the complex are highly phosphorylated by protein kinase C (0.5-0.9 mol of phosphate/mol of subunit), while EF-1 alpha is phosphorylated to a lesser extent (0.2 mol/mol). However, the isolated EF-1 alpha subunit is highly phosphorylated (2.0 mol/mol). Phosphopeptide mapping of EF-1 alpha shows that the same sites are modified by protein kinase C in vitro and in PMA-treated cells. Phosphorylation of the valyl-tRNA synthetase.EF-1 complex results in a 3-fold increase in activity of EF-1 as measured by poly(U)-directed polyphenylalanine synthesis; no effect of phosphorylation is detected with valyl-tRNA synthetase and isolated EF-1 alpha. Thus, phosphorylation and activation of EF-1 by protein kinase C, which has been shown to occur in vitro as well as in reticulocytes, may have a role in PMA stimulation of translational rates.
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PMID:Phosphorylation of elongation factor 1 (EF-1) and valyl-tRNA synthetase by protein kinase C and stimulation of EF-1 activity. 206 27

A fragment of the cDNA encoding a rat valyl-tRNA synthetase (TrsVal)-like protein was cloned from a rat cDNA library in lambda gt11 using an oligodeoxyribonucleotide (oligo) probe. Three independent plaque clones containing the human TrsVal cDNA were then isolated from a lambda gt10 human erythroleukemia cDNA library using the rat cDNA fragment as the hybridization probe. Sequence analyses of the cDNA fragments provided a 3.2-kb sequence with an open reading frame that contained the 'HIGH' synthetase signature sequence and the tRNA 3'-end-binding motif, KMSKS, and putative Val-binding motif, EWCISRQ. The sequence was extended to the 3' end of the cDNA by the polymerase chain reaction using an internal primer and an oligo(dT) adapter. The deduced 1051-amino-acid sequence shares 65% identity with yeast TrsVal, and contains a highly basic N-terminal region, a newly evolved protease-sensitive region in sequence close to the C terminus, and several sites for protein kinase C phosphorylation. A 3-kb cDNA fragment was sub-cloned into plasmid pSVL and expressed in COS-7 cells; up to a sevenfold increase in TrsVal activity was obtained. These results confirm the cloning and sequencing of a human TrsVal-encoding cDNA.
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PMID:Cloning, sequencing and expression of a cDNA encoding mammalian valyl-tRNA synthetase. 842 57

Phosphorylation of the alpha, beta and delta subunits of elongation factor (EF) 1 by protein kinase C results in stimulation of elongation activity up to threefold both in vivo and in vitro [Venema, R. C., Peters, H. I. & Traugh, J. A. (1991) J. Biol. Chem. 266, 11,993-11,998, Venema, R. C., Peters, H. I. & Traugh, J. A. (1991) J. Biol. Chem. 266, 12,574-12,580]. The alpha subunit catalyzes the GTP-dependent binding of amino-acyl-tRNA to the ribosome, while the beta gamma and delta subunits of EF-1 catalyze exchange of the residual GDP on EF-1 alpha for GTP. To determine whether the change in elongation rate following phosphorylation by protein kinase C is due to stimulation of GDP/GTP exchange activity, EF-1 and EF-1.valyl-tRNA-synthetase have been purified from rabbit reticulocytes, phosphorylated in vitro by protein kinase C and the effect of phosphorylation on nucleotide-exchange activity analyzed. The alpha, beta and delta subunits are phosphorylated only on serine, and phosphopeptide maps show distinct phosphopeptides for each subunit. Following quantitative phosphorylation of EF-1 by protein kinase C on the alpha, beta, and delta subunits, a twofold enhancement of the rate of nucleotide exchange over the non-phosphorylated controls is observed with EF-1 and EF-1.valyl-tRNA synthetase. Stimulation of nucleotide exchange results in a two-fold increase in the formation of EF-1 alpha.GTP.Phe-tRNA, leading to an increased rate of binding of Phe-tRNA to ribosomes. The magnitude of stimulation of the exchange rate is similar to that reported previously for the rate of elongation following phosphorylation of EF-1 by protein kinase C. Thus, the enhancement of EF-1 activity in response to 4 beta-phorbol 12-myristate 13-acetate appears to be due to stimulation of the rate of GDP/GTP exchange following phosphorylation of EF-1 by protein kinase C.
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PMID:Phosphorylation of elongation factor 1 (EF-1) by protein kinase C stimulates GDP/GTP-exchange activity. 853 2

The eukaryotic guanine-nucleotide exchange factor commonly called elongation factor-1 betagammadelta (EF-1betagammadelta), comprises four different subunits including valyl-tRNA synthetase (EF-1betagammadelta/ValRS). The factor is multiply-phosphorylated by three different protein kinases, protein kinase C, casein kinase II and cyclin dependent kinase 1 (CDKI). EF-1betagammadelta/ValRS is organized as a macromolecular complex for which we propose a new structural model. Evidence that EF-1betagammadelta/ValRS is a sophisticated supramolecular complex containing many phosphorylation sites, makes it a potential regulator of any of the functions of its partner EF-1alpha, not only involved in protein synthesis elongation, but also in many other cellular functions.
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PMID:Multiple phosphorylation sites and quaternary organization of guanine-nucleotide exchange complex of elongation factor-1 (EF-1betagammadelta/ValRS) control the various functions of EF-1alpha. 979 84