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

Int Immunol. 2000 Oct;12(10):1389-96. doi: 10.1093/intimm/12.10.1389.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • 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*
  • cdc25 Phosphatases / physiology

Substances

  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Pim1 protein, mouse
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-pim-1
  • Mitogen-Activated Protein Kinases
  • Cdc25a protein, mouse
  • cdc25 Phosphatases