Regulation of eukaryotic translation initiation factor expression during T-cell activation.
Primary T-cells are metabolically quiescent, with little DNA, RNA or protein synthesis. Upon mitogenic stimulation the rate of protein synthesis increases 10-fold. We have studied the role of eIF-2 and eIF-4 alpha (eIF-4E) expression in the mechanism of translational activation. During this period, the levels of eIF-2 alpha and eIF-4 alpha mRNA increase some 50-fold. Similar to the increase in ribosomes and mRNA, the number of eIF-2 alpha, eIF-2 beta, and eIF-4 alpha molecules per cell also increase 2-3-fold. This suggests that in addition to an increase in the pool size of translational components, an additional mechanism exists which results in an increased efficiency of factor utilization. We have looked at initiation factor phosphorylation. We find that eIF-2 alpha does not undergo significant changes in its phosphorylation state nor is there a change in the efficiency of eIF-2 utilization. However, there is a rapid increase in the phosphorylation state of eIF-4 alpha which correlates with the rapid increase in translational activity. It thus appears there are 2 distinct components responsible for the translational activation of quiescent T-cells during mitogenic stimulation. The first is the phosphorylation of eIF-4 alpha, with a concomitant increase in the efficiency of eIF-4 alpha utilization. The second is an increase in the pool sizes of eIF-2 and eIF-4 alpha.
Boal
T R
TR
Molecular Hematology Branch, NHLBI, NIH, Bethesda, MD 20892.
Chiorini
J A
JA
Cohen
R B
RB
Miyamoto
S
S
Frederickson
R M
RM
Sonenberg
N
N
Safer
B
B
D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D010448:Peptide Initiation Factors / Q000096:biosynthesis / Q000235:genetics*; D010766:Phosphorylation; D010835:Phytohemagglutinins; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate
D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate