Interleukin-2 Activation of Intracellular Signaling Pathways
Effects on Gene Expression, Proliferation, and Apoptosis
Description:... During an immune reaction, T cell clones must be expanded by mitogenic cytokines such as interleukin-2 (IL-2). IL-2 is able to induce proliferation, protection from apoptosis, and differentiation of T cells. These cellular phenomena are mediated through signaling events initiated at the IL-2 receptor (IL-2R) and are associated with changes in the mRNA levels that encode necessary proteins. The following work examined the molecular signals initiated at the IL-2R and sought to understand their linkage to increases in mRNA levels and subsequent cellular responses, such as proliferation and protection from apoptosis. Understanding these links is vital to understanding the molecular events that control the immune response, as well as providing insight into the cell cycle and activated transcription. To study this problem, an IL-2 responsive system based on thymic blast cells (TBCs) was developed and characterized. This system has the advantage of yielding a large number of IL-2 responsive cells from primary human tissue. Using the TBCs it was shown that transcription of important cell cycle genes is linked to the IL-2R via the c-Ras/MAPK pathway. Additionally, this pathway is responsible for IL-2 mediated proliferation. A second pathway, mediated through PKC, is responsible for upregulation of anti-apoptosis genes and protection from apoptosis. TBCs were also used to show that IL-2 can increase mRNA levels of specific genes by releasing transcriptional attenuation. Together these results show that specific signaling pathways can be linked to increases in specific mRNAs and suggest at least one mechanism of this upregulation. These results also show that increased expression of certain mRNAs may explain specific cellular responses. Finally, this work provides direction for future research that should yield more interesting insights into IL-2 mediated control of transcription.
Show description