Rapamycin-induced inhibition of p34cdc2 kinase activation is associated with G1/S-phase growth arrest in T lymphocytes.

摘要: The macrolide rapamycin (RAP) is a potent inhibitor of interleukin-2 (IL-2)-induced T-cell proliferation. Current models suggest that RAP, when complexed to its intracellular receptor, FK506-binding protein, interferes with an IL-2 receptor-coupled signaling pathway required for cell-cycle progression from G1- S-phase. Here we show RAP treatment inhibits the growth IL-2-dependent cytotoxic line, CTLL-2, in late G1-phase, just prior entry cells into In contrast, RAP-treated CTLL-2 retained ability respond enhanced cytolytic activity, indicating was not general suppressant cellular responsiveness IL-2. Subsequent studies revealed stimulation triggered delayed activation p34cdc2 kinase, timing which correlated S-phase transition. increase kinase activity blocked by RAP. sensitivity mechanism implicates this control commitment IL-2-stimulated T-cells.