C-FOS GENE INDUCTION BY INTERLEUKIN-2 - IDENTIFICATION OF THE CRITICAL CYTOPLASMIC REGIONS WITHIN THE INTERLEUKIN-2 RECEPTOR-BETA CHAIN

Interleukin 2 (IL-2) plays a critical role in the growth and differentiation of lymphoid cells. The IL-2 signal is delivered intracellularly by the IL-2 receptor beta-chain (IL-2R-beta); however, the mechanism by which the signal reaches the nucleus remains unclear. In this study, we demonstrate the rapid activation of c-fos protooncogene transcription by IL-2 and provide evidence that the serum-responsive element (SRE) within the c-fos promoter is responsible for the activation in a murine pro-B-cell line, BAF-B03, expressing the human IL-2R-beta cDNA. Interestingly, the same SRE is also responsible for c-fos gene activation by interleukin 3 or erythropoietin. Further, we show that the activation of c-fos by IL-2 requires defined cytoplasmic regions of IL-2R-beta-i.e., the "serine-rich" region, which is known to be essential for growth-signal transduction in BAF-B03 cells, and the "acidic region," which is located more distal to the cell membrane. These results indicate the functional importance of the two distinct regions within the IL-2R-beta cytoplasmic domain in IL-2-induced c-fos gene activation and point to a potential role of the acidic region in IL-2 signal transduction that could not be adequately assessed in a previous study.