Covering a Broad Dynamic Range: Information Processing at the Erythropoietin Receptor
Covering a Broad Dynamic Range: Information Processing at the Erythropoietin Receptor
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DOI：
10.1126/science.1184913
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发表时间：
2010-06-11
期刊：
影响因子：
56.9
通讯作者：
Klingmueller, Ursula
中科院分区：
文献类型：
--
作者：
Becker, Verena;Schilling, Marcel;Klingmueller, Ursula
细胞表面受体将细胞外信号转化为受体激活，从而触发细胞内信号网络并控制细胞决策。一个主要的未解决的问题是鉴定受体的性质，关键决定处理配体编码的信息。我们通过定量数据的数学建模和实验验证表明，细胞表面受体的快速配体耗竭和补充是促红细胞生成素受体（Epo）的特征。Epo-EpoR复合物的数量和EpoR激活随时间的增加与配体的输入呈线性关系；这个过程可以在很大的配体浓度范围内进行。这种关系完全依赖于与配体结合无关的EpoR周转，这表明细胞内大型受体库的重要作用。这些受体的特性使系统能够应对造血系统的基础和急性需求。
Cell surface receptors convert extracellular cues into receptor activation, thereby triggering intracellular signaling networks and controlling cellular decisions. A major unresolved issue is the identification of receptor properties that critically determine processing of ligand-encoded information. We show by mathematical modeling of quantitative data and experimental validation that rapid ligand depletion and replenishment of the cell surface receptor are characteristic features of the erythropoietin (Epo) receptor (EpoR). The amount of Epo-EpoR complexes and EpoR activation integrated over time corresponds linearly to ligand input; this process is carried out over a broad range of ligand concentrations. This relation depends solely on EpoR turnover independent of ligand binding, which suggests an essential role of large intracellular receptor pools. These receptor properties enable the system to cope with basal and acute demand in the hematopoietic system.