Bauer J H, Liu K D, You Y, Lai S Y, Goldsmith M A
Institute for Biochemistry, Free University Berlin, 14195 Berlin, Germany.
J Biol Chem. 1998 Apr 10;273(15):9255-60. doi: 10.1074/jbc.273.15.9255.
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-9Ralpha and the common gammac 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-9Ralpha and the membrane-proximal segment of gammac 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-1, 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-5 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-9R and its specific connections to various biologic responses.
白细胞介素-9（IL-9）是一种对肥大细胞和T细胞系具有多效性作用的细胞因子。它通过由IL-9Rα和共同的γc亚基组成的IL-9R复合物发挥作用。在此，我们报告了受体异源二聚化以实现有效信号转导的功能证据，并确定了IL-9R功能在两个受体亚基中的最低要求。IL-9Rα的酪氨酸336和γc的膜近端片段对信号传导都至关重要。活化的IL-9R复合物利用Janus激酶JAK1和JAK3来随后激活信号转导子和转录激活因子（STAT）因子STAT-1、STAT-3和STAT-5。这个过程不依赖于Tyk2。我们进一步证明，活化的STAT复合物由STAT-1和STAT-5同二聚体以及STAT-1-STAT-3异二聚体组成。最后，我们表明T细胞系中的IL-9R信号传导不会导致可检测到的丝裂原活化蛋白激酶激活，并导致增殖不能持续。尽管如此，这些T细胞能有效免受地塞米松诱导的细胞凋亡。这些结果进一步明确了IL-9R的分子结构及其与各种生物学反应的特定联系。
