Heteromerization of the γc chain with the interleukin-9 receptor α subunit leads to STAT activation and prevention of apoptosis
Heteromerization of the γc chain with the interleukin-9 receptor α subunit leads to STAT activation and prevention of apoptosis
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DOI：
10.1074/jbc.273.15.9255
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发表时间：
1998-04-10
影响因子：
4.8
通讯作者：
Goldsmith, MA
中科院分区：
文献类型：
--
作者：
Bauer, JH;Liu, KD;Goldsmith, MA
白介素 9 (IL-9) 是一种对肥大细胞和 T 细胞系具有多效作用的细胞因子。它通过由 IL-9R α 和共同的 γ(c) 亚基组成的 IL-9R 复合物发挥其作用。在这里，我们报告了受体异聚化以实现有效信号转导的功能证据，并且我们定义了 IL-9R 功能的两个受体亚基（IL-9R α 的酪氨酸 336 和 IL-9R α 的近膜片段）的最低要求。 gamma(c) 对于信号传导都至关重要。激活的 IL-9R 复合物利用 Janus 激酶 JAK1 和 JAK3 来随后激活信号转导器和激活转录 (STAT) 因子 STAT-1、STAT-3 和 STAT-5。此过程独立于 Tyk2。我们进一步证明激活的 STAT 复合物由 STAT-1 和 STAT-B 同二聚体以及 STAT-1-STAT-3 异二聚体组成。最后，我们证明 T 细胞系中的 IL-9R 信号传导不会导致可检测的丝裂原激活蛋白激酶激活，并导致不持续的增殖。尽管如此，这些 T 细胞得到了有效的保护，免受地塞米松诱导的细胞凋亡。这些结果进一步定义了 IL-SR 的分子结构及其与各种生物反应的具体联系。
Interleukin-9 (IL-9) is a cytokine with pleiotropic effects on mast cell and T cell lines. It exerts its effects through the IL-9R complex consisting of IL-9R alpha and the common gamma(c) subunit, Here we report functional evidence for receptor heteromerization for efficient signal transduction, and we define minimal requirements in the two receptor subunits for IL-9R function, Tyrosine 336 of the IL-9R alpha and the membrane-proximal segment of gamma(c) are both crucial for signaling. The activated IL-9R complex employs the Janus kinases JAK1 and JAK3 for subsequent activation of the signal transducer and activator transcription (STAT) factors STAT-I, STAT-3, and STAT-5. This process is independent of Tyk2. We demonstrate further that the activated STAT complexes consist of STAT-1 and STAT-B homodimers and STAT-1-STAT-3 heterodimers. Finally, we show that IL-9R signaling in a T cell line does not result in detectable mitogen-activated protein kinase activation and leads to unsustained proliferation. Nonetheless, these T cells are efficiently protected from dexamethasone-induced apoptosis. These results further define the molecular architecture of the IL-SR and its specific connections to various biologic responses.