Identification of three distinct receptor binding sites of murine interleukin-11
Identification of three distinct receptor binding sites of murine interleukin-11
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DOI：
10.1074/jbc.274.9.5755
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发表时间：
1999-02-26
影响因子：
4.8
通讯作者：
Heath, JK
中科院分区：
文献类型：
--
作者：
Barton, VA;Hudson, KR;Heath, JK
白介素 11 (IL-11) 是细胞因子 gp130 家族的成员。这些细胞因子驱动多亚基受体复合物的组装，所有这些复合物都含有至少一个跨膜信号受体 gp130 分子。 IL-11 和 IL-11 受体 (IL-11R) 的复合物已被证明能够以高亲和力与 gp130 相互作用，并诱导 gp130 依赖性信号传导。在这项研究中，我们通过检查 mIL-11 突变体在受体结合和细胞增殖测定中的活性，确定了对鼠 IL-11 (mIL-11) 与 IL-11R 和 gp130 结合至关重要的残基。根据结构研究和 IL-11 模型的预测，这些残基的位置表明 mIL-11 具有三个不同的受体结合位点。它们在结构和功能上类似于之前定义的白介素 6 (IL-6) 受体结合位点 I、II 和 III。这支持了 IL-11 通过形成六聚体受体复合物发出信号的假设，并表明位点 III 是通过与 gp130 关联发出信号的细胞因子的一般特征。
Interleukin-11 (IL-11) is a member of the gp130 family of cytokines. These cytokines drive the assembly of multisubunit receptor complexes, all of which contain at least one molecule of the transmembrane signaling receptor gp130. A complex of IL-11 and the IL-11 receptor (IL-11R) has been shown to interact with gp130, with high affinity, and to induce gp130- dependent signaling. In this study, we have identified residues crucial for the binding of murine IL-11 (mIL-11) to both the IL-11R and gp130 by examining the activities of mIL-11 mutants in receptor binding and cell proliferation assays. The location of these residues, as predicted from structural studies and a model of IL-11, reveals that mIL-11 has three distinct receptor binding sites. These are structurally and functionally analogous to the previously defined receptor binding sites I, II, and III of interleukin-6 (IL-6). This supports the hypothesis that IL-11 signals via the formation of a hexameric receptor complex and indicates that site III is a generic feature of cytokines that signal via association with gp130.