부산대학교 도서관

We have shown previously that serum promotes T cell proliferation by acting with T cell receptor (TCR) agonists to efficiently down-regulate p27Kip1and activate cdk2-containing complexes. In the studies described here, the effect of serum on the expression of the α subunit of the interleukin-2 receptor (IL-2Rα) was examined. We found that serum was required for maximal and sustained IL-2Rα protein expression and consequent IL-2 signaling in TCR-activated splenocytes. Serum had no effect on IL-2Rα mRNA levels and thus modulates IL-2Rα expression post-transcriptionally. Unlike wild-type splenocytes, splenocytes exhibiting serum-independent cdk2 activation due to loss of p27Kip1efficiently expressed IL-2Rα in serum-deficient medium. Conversely, serum did not promote IL-2Rα accumulation in conditions in which cdk2 activity was blocked. These findings demonstrate that cdk2 activation is necessary and sufficient for IL-2Rα accumulation in TCR-stimulated splenocytes. On the other hand, IL-2 signaling was required (at least in part) for cdk2 activation in these cells. Thus, cdk2 activation, IL-2Rα expression, and IL-2 signaling are interdependent events, and we suggest that this feed-forward regulatory loop plays a key role in T cell mitogenesis.