The effect of IL-2 on the expression of the mouse zinc-fingers and homeoboxes 1 (ZHX1) gene was investigated in a mouse cytotoxic T cell line, CTLL-2 cells. IL-2 specifically induced the expression of ZHX1 mRNA. The level of ZHX1 mRNA was decreased in the absence of IL-2. These alterations were in parallel with the status of cell proliferation. The signaling pathways involved in the induction were examined. AG-490, wortmannin, and LY294002 blocked the induction by IL-2. Nuclear run-on assays and a mRNA stability analysis revealed that the half-life of ZHX1 mRNA but not the transcription rate of the gene was increased by IL-2. Thus, we conclude that IL-2 induces the expression of the mouse ZHX1 gene in CTLL-2 cells, that both Janus kinase 3/signal transducer and activator of transcription 5 and phosphoinositide 3-kinase pathways are involved in the induction, and that the increased mRNA stability results in the induction.