The Pim-1 kinase stimulates maturation of TCRbeta-deficient T cell progenitors: implications for the mechanism of Pim-1 action

• Published in: International immunology Vol. 12; no. 10; pp. 1389 - 1396
• Main Authors: Leduc, I, Karsunky, H, Mathieu, N, Schmidt, T, Verthuy, C, Ferrier, P, Möröy, T
• Format: Journal Article
• Language: English
• Published: England 01-10-2000
• Subjects: Alleles; Animals; cdc25 Phosphatases - physiology; Cell Cycle; Hematopoietic Stem Cells - physiology; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases - physiology; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-pim-1; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - physiology; T-Lymphocytes - physiology
• ISSN: 0953-8178

We demonstrate that overexpression of Pim-1, a cytoplasmic serine/threonine kinase of poorly defined function, results in the development of substantial numbers of CD4(+)CD8(+) double-positive thymocytes in two independent knock-out mouse models (i.e. the RAG-1-deficient and TCRbeta gene enhancer-deleted mice) in which production of a functionally rearranged TCRbeta gene (hence the pre-TCR) is impaired. This activity of Pim-1, however, does not affect signaling through the Ras/Raf/MAP kinase cascade nor signaling which mediates suppression of TCRbeta gene recombination (i.e. allelic exclusion). While overexpression of Pim-1 positively affects cell cycle progression in selected CD4(-)CD8(-) double-negative precursors, it did not affect expression of components of the cell cycle machinery, with the exception of the G(1)-specific phosphatase Cdc25A upon antigen receptor stimulation. We propose that Pim-1 acts downstream, or in parallel, to pre-TCR-mediated selection as one factor involved in the proliferative expansion of beta-selected pre-T cells.