EXPRESSION OF THE PIM-1 PROTOONCOGENE - DIFFERENTIAL INDUCIBILITY BETWEEN ALPHA BETA-T-CELLS AND GAMMA/DELTA-T-CELLS AND B-CELLS/

The pim-1 gene encodes a serine/threonine protein kinase with expressi on restricted primarily to cells of hematopoietic lineage and is thoug ht to play a role in the signal transduction events associated with ly mphocyte activation. A rapid increase in pim-1 mRNA levels was found a fter stimulation of normal unseparated PBMCs with phorbol ester (PMA) and a calcium ionophore (ionomycin) with the peak level occurring 4 hr poststimulation. Treatment of PBMCs with ionomycin alone caused only a minimal increase in pim-1 mRNA, whereas treatment with PMA alone ind uced a large increase in pim-1 mRNA, suggesting that the activation of a signaling pathway involving protein kinase C is responsible for the accumulation of this transcript. In enriched subpopulations of restin g alpha/beta-T cells, gamma/delta-T cells, and B cells, pim-1 expressi on was found to be constitutively expressed, albeit at lower levels in T cells. This basal level of pim-1 expression could be increased by s timulation of alpha/beta-T cells (approx fivefold) and gamma/delta-T c ells (similar to sevenfold) with PMA plus ionomycin. In contrast, pim- 1 expression was not inducible in B cells. In PBMCs, half-life determi nation studies showed that turnover of pim-1 mRNA was markedly prolong ed as a result of message stabilization induced by PMA plus ionomycin treatment. In addition, stable pim-1 transcripts were also observed in all transformed lymphoid cell lines examined. Taken together, these r esults suggest that the stability of pim-1 transcripts may be linked t o the regulation of cell growth and represent the first direct demonst ration that pim-1 expression is indeed regulated in a cell-type-specif ic manner. (C) 1995 Academic Press, Inc.