The human epidermal growth factor receptor (HER) system is an intricately regulated system that plays critical roles in development and tumorigenesis. Here, we apply integrated experimentation and modeling to analyze HER receptor activation in a panel of cell lines expressing endogenous levels of EGFR/HER1 and different levels of HER2. A mathematical model that includes the fundamental processes involved in receptor activation and trafficking was used to fit the experimental data, and values of the independent parameters for active receptor dimer formation affinities, trafficking rates and relative phosphorylation levels were estimated. Obtained parameter values quantitatively support the existing ideas on the effect of HER2 on EGFR dynamics, and enable us to predict the abundances of various phosphorylated receptor dimers in the cell lines.

译文

:人类表皮生长因子受体(HER)系统是一个复杂的调控系统,在发育和肿瘤发生中起着至关重要的作用。在这里,我们应用综合实验和建模来分析一组表达内源性EGFR / HER1和不同水平HER2的细胞系中的HER受体激活。使用包括参与受体激活和运输的基本过程的数学模型来拟合实验数据,并估计活性受体二聚体形成亲和力,运输速率和相对磷酸化水平的独立参数的值。获得的参数值定量支持关于HER2对EGFR动力学影响的现有观点,并使我们能够预测细胞系中各种磷酸化受体二聚体的丰度。

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