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98667 DRAK2 Negatively Regulates T Cell Receptor Signaling by Increasing the Threshold for T Cell Activation Shanty Wijaya Mentor: Craig Walsh T cells play a central role in controlling acquired immune response. Regulatory molecules expressed in T cells participate in setting the threshold for T cell activation and limit the response via negative feedback regulation; hence, these molecules maintain T cell homeostasis. DRAK2 (DAP-related apoptotic kinase-2) is a regulatory molecule that is expressed in T cells and is found exclusively in lymphoid tissue. Kinases are known to have essential roles in lymphocyte activation and apoptotic signaling, however, the regulation of intracellular signaling pathways is still not completely known. T cells from DRAK2-/- mice have been shown to exhibit an increase in sensitivity to T Cell Receptor (TCR) signaling and receive a greater intensity of TCR signal, resulting in an enhanced calcium flux (calcium is an essential signal for T cell development and activation). Based on this understanding (via an in vivo model), we hypothesize that DRAK2 negatively regulates T cell receptor signaling by directly modulating calcium mobilization. An alternative hypothesis is that DRAK2 alters the development/homeostasis of T cell populations in vivo. To discriminate between these two models, I sought to knock down the expression of DRAK2 in an established E61 Jurkat T cell line using an RNAi approach. Calcium flux of DRAK2 knock-down E61 T cells and wild type E61 T cells were then analyzed by calcium flux assays. Calcium flux in DRAK2 knock-down E61 T cells was expected to be significantly higher than E61 wild type T cells, which would provide proof that DRAK2 directly modulates TCR signaling.