Medicine and Health Sciences Commons^™

Rapamycin-Induced Inhibition Of P34(Cdc2) Kinase Activation Is Associated With G1/S-Phase Growth Arrest In T Lymphocytes, W. G. Morice, Gregory J. Brunn, Gregory Wiederrecht, John Siekierka, R. T. Abraham

Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works

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- to S-phase. Here we show that RAP treatment inhibits the growth of an IL-2-dependent cytotoxic T-cell line, CTLL-2, in late G1- phase, just prior to entry of the cells into S-phase. In contrast, RAP- treated CTLL-2 cells retained the ability to respond to IL-2 with enhanced cytolytic activity, indicating that RAP was not a general suppressant of cellular responsiveness to …