INTERLEUKIN-2 SIGNALING INVOLVES THE PHOSPHORYLATION OF STAT PROTEINS
INTERLEUKIN-2 SIGNALING INVOLVES THE PHOSPHORYLATION OF STAT PROTEINS
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DOI：
10.1073/pnas.92.17.7779
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发表时间：
1995-08-15
影响因子：
11.1
通讯作者：
GREENBERG, ME
中科院分区：
文献类型：
--
作者：
FRANK, DA;ROBERTSON, MJ;GREENBERG, ME
参与免疫反应调节的最重要的细胞因子之一是白细胞介素 2 (IL-2)，它是 T 淋巴细胞和自然杀伤细胞增殖和功能的有效激活剂。IL-2 的作用在细胞内传播的机制尚不清楚。虽然最近显示 IL-2 与其受体的结合可导致两种激酶 Jak-1 和 Jak-3 的激活，但导致特定基因激活的细胞核信号传导途径中的后续步骤尚未明确。由于许多激活 Jak 激酶的细胞因子也会导致酪氨酸磷酸化和 Stat 转录因子家族成员的激活，因此检查了 IL-2 触发 Stat 磷酸化的能力。活化的人 T 淋巴细胞或自然杀伤细胞系 (NKL) 暴露于 IL-2 会导致 Stat1 α、Stat1 β 和 Stat3 以及两种 Stat 相关蛋白 p94 和 p95 磷酸化。 p94 和 p95 在磷酸化位点和 Src 同源 2 (SH2) 结构域中与 Stat1 具有同源性，但在其他方面与 Stat1 的免疫学不同。这些 Stat 蛋白被发现易位到细胞核并与特定的 DNA 序列结合。这些发现表明，IL-2 与其受体结合可能激活参与免疫细胞功能的特定基因。
One of the most important cytokines involved in immune response regulation is interleukin 2 (IL-2), a potent activator of the proliferation and function of T lymphocytes and natural killer cells, The mechanisms by which the effects of IL-2 are propagated within cells are not understood, While the binding of IL-2 to its receptor was recently shown to lead to the activation of two kinases, Jak-1 and Jak-3, subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized, Since many cytokines that activate Jak kinases also lead to the tyrosine phosphorylation and activation of members of the Stat family of transcription factors, the ability of IL-2 to trigger Stat phosphorylation was examined. Exposure of activated human T lymphocytes or of a natural killer cell line (NKL) to IL-2 leads to the phosphorylation of Stat1 alpha, Stat1 beta, and Stat3, as well as of two Stat-related proteins, p94 and p95. p94 and p95 share homology with Stat1 at the phosphorylation site and in the Src homology 2 (SH2) domain, but otherwise are immunologically distinct from Stat1, These Stat proteins were found to translocate to the nucleus and to bind to a specific DNA sequence. These findings suggest a mechanism by which IL-2 binding to its receptor may activate specific genes involved in immune cell function.