Expression of the pim-1 protooncogene: differential inducibility between alpha/beta- and gamma/delta-T cells and B cells.
The pim-1 gene encodes a serine/threonine protein kinase with expression restricted primarily to cells of hematopoietic lineage and is thought to play a role in the signal transduction events associated with lymphocyte activation. A rapid increase in pim-1 mRNA levels was found after 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 induced 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 resting alpha/beta-T cells, gamma/delta-T cells, and B cells, pim-1 expression was found to be constitutively expressed, albeit at lower levels in T cells. This basal level of pim-1 expression could be increased by stimulation of alpha/beta-T cells (approx fivefold) and gamma/delta-T cells (approximately sevenfold) with PMA plus ionomycin. In contrast, pim-1 expression was not inducible in B cells. In PBMCs, half-life determination studies showed that turnover of pim-1 mRNA was markedly prolonged 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 results suggest that the stability of pim-1 transcripts may be linked to the regulation of cell growth and represent the first direct demonstration that pim-1 expression is indeed regulated in a cell-type-specific manner.
Wingett
D
D
Department of Microbiology, Washington State University, Pullman, 99164-4233, USA.
Stone
D
D
Davis
W C
WC
Magnuson
N S
NS
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D005434:Flow Cytometry; D015759:Ionomycin / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1; D012333:RNA, Messenger / Q000096:biosynthesis / Q000737:chemistry; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015759:Ionomycin; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1; D013755:Tetradecanoylphorbol Acetate