Identification and purification of human Stat proteins activated in response to interleukin-2

J Hou, U Schindler, WJ Henzel, SC Wong, SL McKnight - Immunity, 1995 - cell.com
J Hou, U Schindler, WJ Henzel, SC Wong, SL McKnight
Immunity, 1995cell.com
A key cytokine induced during the immune response is 11-2. Following T cell activation, the
genes encoding IL-2 and ths varlouschains of lta receptor are transcrip tionally induced. In
turn, secreted IL-2 serves to stimulate the proliferation and dlfferentiatlon of T lymphocytes.
Several recent studies have implicated Jak kinases in the signallng pathway induced by IL-
2. Following this lead, we set out to identtfy tmnacrlption factors induced in response to 11-2.
Human peripheral blood lymphocytes were observed to contain several IL-24nduclble DNA …
Summary
A key cytokine induced during the immune response is 11-2. Following T cell activation, the genes encoding IL-2 and ths varlouschains of lta receptor are transcrip tionally induced. In turn, secreted IL-2 serves to stimulate the proliferation and dlfferentiatlon of T lymphocytes. Several recent studies have implicated Jak kinases in the signallng pathway induced by IL-2. Following this lead, we set out to identtfy tmnacrlption factors induced in response to 11-2. Human peripheral blood lymphocytes were observed to contain several IL-24nduclble DNA binding activities. Similar activities were also observed in a transformed human lymphocyte line, termed YT. We have purlfied these activities and found that the principal IL-Plnducible component beam signlftcant relatedness to a prolactin-induced tmnscriptton factor flmt identtfled in sheep mammary gland tissue. We hypothesize that acttvatlon of this protein, deslgnated hStat5, helps govern the biological effects of IL-2 during the immune response. lntroductlon
Acting through a high affinity multisubunit receptor, interleukin-2 (IL-2) stimulates the proliferation and differentiated function of hematopoietic cells (Taniguchi et al., 1988; Smith, 1988; Taniguchi and Minami, 1993; Waldmann, 1993). Considerable progress has been made during the past decade on the biological effects of IL-2 as well as the molecular composition of the cytokine and its cognate receptor. Cells bearing the functional receptor complex respond to IL-2 via at least two distinctive pathways. Theycommonlyenter a proliferative state facilitating significant autocrine expansion. IL-2 can also cause receptor-bearing lymphocytes to mature along variousdifferentiative pathways, including those leading to cytolytic and immune helper cell function. The intracellular signaling and gene regulatory circuitry controlled by IL-2 is, however, only beginning to be resolved. Perhaps the most useful information pertaining to the latter challenge has come from studies of the IL-2 receptor. Functional IL-2 receptor is a heterotrimeric complex composed of polypeptide chains designated IL-2Ra, IL-2Rf3, and IL-2Rr (Cosman et al., 1984; Leonard et al., 1984; Nikaido et al., 1984; Hatakeyama et al., 1989; Takeshita et al., 1992; Voss et al., 1993). The IL-2Ra chain
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