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

We demonstrate that overexpression of Pim-1, a cytoplasmic serine/threonine kinase of poorly defined function, results in the development of substanti al numbers of CD4(+)CD8(+) double-positive thymocytes in two independent kn ock-out mouse models (i.e, the RAG-1-deficient and TCR beta gene enhancer-d eleted mice) in which production of a functionally rearranged TCR beta gene thence the preTCR) is impaired. This activity of Pim-1, however, does not affect signaling through the Ras/Raf/ MAP kinase cascade nor signaling whic h mediates suppression of TCR beta gene recombination (i.e. allelic exclusi on). While overexpression of Pim-1 positively affects cell cycle progressio n in selected CD4(-)CD8(-) double-negative precursors, it did not affect ex pression of components of the cell cycle machinery, with the exception of t he G(1)-specific phosphatase Cdc25A upon antigen receptor stimulation. We p ropose that Pim-1 acts downstream, or in parallel, to pre-TCR-mediated sele ction as one factor involved in the proliferative expansion of beta-selecte d pre-T cells.