Interleukin-2, Interleukin-15, and Their Receptors

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Abstract
Both IL-15 and 1L-2 are 14–15 kDa members of the four α-helical bundle family of cytokines that have T cell growth factor activity. In contrast to the pattern manifested by IL-2, IL-15 mRNA is produced by a wide variety of tissues other than T cells. We have demonstrated that IL-15 expression is post-transcriptional regulated by multiple elements, including the ten upstream AUGs of the 5′ UTR, a 48aa signal peptide and the carboxyterminus of the mature protein. IL-15 utilizes two distinct receptor signaling pathways. In T cells the IL-15 receptor includes IL-2Rβ and γc subunits shared with IL-2 as well as an IL-15 specific receptor, IL-15Rα. However, mast cells respond to IL-15 using a receptor system that does not share elements with the IL-2R system but involves a novel 60–65kDa IL-15RX subunit. In mast cells, IL-15 signaling involves JAK-2 and STAT-5 activation rather than the JAK-1 and JAK-3 as well as the STAT-3 and STAT-5 used by both IL-2 and IL-15 in activated T cells.