The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes.
BACKGROUND
Activation of human resting T lymphocytes results in an immediate increase in protein synthesis. The increase in protein synthesis after 16-24 h has been linked to the increased protein levels of translation initiation factors. However, the regulation of protein synthesis during the early onset of T cell activation has not been studied in great detail. We studied the regulation of protein synthesis after 1 h of activation using alphaCD3 antibody to stimulate the T cell receptor and alphaCD28 antibody to provide the co-stimulus.


RESULTS
Activation of the T cells with both antibodies led to a sustained increase in the rate of protein synthesis. The activities and/or phosphorylation states of several translation factors were studied during the first hour of stimulation with alphaCD3 and alphaCD28 to explore the mechanism underlying the activation of protein synthesis. The initial increase in protein synthesis was accompanied by activation of the guanine nucleotide exchange factor, eukaryotic initiation factor (eIF) 2B, and of p70 S6 kinase and by dephosphorylation of eukaryotic elongation factor (eEF) 2. Similar signal transduction pathways, as assessed using signal transduction inhibitors, are involved in the regulation of protein synthesis, eIF2B activity and p70 S6 kinase activity. A new finding was that the p38 MAPK alpha/beta pathway was involved in the regulation of overall protein synthesis in primary T cells. Unexpectedly, no changes were detected in the phosphorylation state of the cap-binding protein eIF4E and the eIF4E-binding protein 4E-BP1, or the formation of the cap-binding complex eIF4F.


CONCLUSIONS
Both eIF2B and p70 S6 kinase play important roles in the regulation of protein synthesis during the early onset of T cell activation.
Kleijn
Miranda
M
Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, MSI/Wellcome Trust Biocentre, DD1 5EH United Kingdom. m.scheperkleijn@dundee.ac.uk
Proud
Christopher G
CG
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D020717:Eukaryotic Initiation Factor-2B; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D010750:Phosphoproteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa