Discovery of a cytokine and its receptor by functional screening of the extracellular proteome
Discovery of a cytokine and its receptor by functional screening of the extracellular proteome
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DOI：
10.1126/science.1154370
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发表时间：
2008-05-09
期刊：
影响因子：
56.9
通讯作者：
Williams, Lewis T.
中科院分区：
文献类型：
--
作者：
Lin, Haishan;Lee, Ernestine;Williams, Lewis T.
为了理解参与细胞-细胞信号传导的分泌蛋白和受体的系统，我们产生了一套全面的重组分泌蛋白和跨膜蛋白的胞外结构域，其构成了胞外空间的大部分蛋白组分。每种蛋白质都在一系列测定中进行了测试，这些测定测量了不同细胞类型中的代谢、生长或转录反应。分析了各试验的响应模式，以确定每种蛋白质的功能选择性程度。其中一种高度选择性的蛋白质是一种以前未描述的配体，称为白细胞介素-34（IL- 34），它刺激单核细胞活力，但不影响广泛的其他测定中的反应。在单独的功能筛选中，我们使用跨膜蛋白的细胞外结构域的集合来发现IL- 34的受体，其是已知的细胞因子受体，集落刺激因子1（也称为巨噬细胞集落刺激因子）受体。因此，这种系统的方法是有用的，发现新的配体和受体，并评估功能的选择性细胞外调节蛋白。
To understand the system of secreted proteins and receptors involved in cell- cell signaling, we produced a comprehensive set of recombinant secreted proteins and the extracellular domains of transmembrane proteins, which constitute most of the protein components of the extracellular space. Each protein was tested in a suite of assays that measured metabolic, growth, or transcriptional responses in diverse cell types. The pattern of responses across assays was analyzed for the degree of functional selectivity of each protein. One of the highly selective proteins was a previously undescribed ligand, designated interleukin- 34 ( IL- 34), which stimulates monocyte viability but does not affect responses in a wide spectrum of other assays. In a separate functional screen, we used a collection of extracellular domains of transmembrane proteins to discover the receptor for IL- 34, which was a known cytokine receptor, colony-stimulating factor 1 ( also called macrophage colony- stimulating factor) receptor. This systematic approach is thus useful for discovering new ligands and receptors and assessing the functional selectivity of extracellular regulatory proteins.