Lymphocyte blastogenesis. Post-transcriptional controls of protein synthesis

To better understand the regulation of macromolecular synthesis in the response of lymphocytes to a mitogen, we have used two-dimensional electrophoresis to search for specificity in the early increase seen in protein synthesis in human lymphocytes treated with phytohemagglutinin and examined the role of new RNA synthesis in this response. Our results confirm a major increase in overall protein synthesis after 4 h of phytohemagglutinin treatment. A further disproportionate increase in the synthetic rates of certain polypeptides was observed using two-dimensional polyacrylamide gel electrophoresis. While actinomycin-D reduced protein synthesis to a level below that of untreated cells, phytohemagglutinin nonetheless enhanced total protein synthesis even in the presence of actinomycin. Some, but not all, of the disproportionate increases in synthesis seen for certain polypeptides are blocked by actinomycin. These results imply the existence of multiple mechanisms controlling protein synthesis early in the course of lymphocyte stimulation. At least some of these do not require new RNA synthesis and thus operate at a post-transcriptional level.