In this work we analyze the flow of information through the Fibroblast Growth Factor Receptor (FGFR) communication channel when different types of signals are transmitted by the MAPK cascade to the gene regulatory network (GRN) formed by the genes C-Myc, DUSP, and Cdc25A, which control fibroblast proliferation. We used the canonical mathematical model of the MAPK cascade coupled to a stochastic model for the activation of the gene regulatory network, subject to different types of FGF inputs (step, quadratic pulses, Dirac delta, and white noise), in order to analyze the response of the gene regulatory network to each type of signal, and determine the temporal variation of the value of its Shannon entropy in each case. Our model suggests that the sustained activation of the FGFR communication channel with a step of FGF > 1 nM is required for cell cycle progression and that during the G1/S transition the amount of uncertainty of the GRN remains at a steady value of ∼ 2.75 bits, indicating that while the fibroblast stimulation with FGF continues the G1/S transition does not require an additional interchange of information between the emitter and the gene regulatory network to be completed. We also found that either low frequency pulses of FGF or low frequency noise, both with a frequency f ≤ 2.77 Hz, are not filtered by the MAPK cascade and can modify the output of the communication channel, i.e., the amount of the effector proteins c-myc, cdc25A and DUSP. An additional effect suggested by our model is that o low frequency periodic signals and noise possibly blockage cell cycle progression because the threshold value concentration of cdc25A for the G1/S transition is not sustained in the in the nucleus during the 10 hours that this process lasts. Finally, from our model we can estimate the capacity of this communication channel in 0.96 bits/min.

中文翻译：

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成纤维细胞生长因子受体通讯通道中的信息流

在这项工作中，我们分析了当不同类型的信号通过 MAPK 级联传递到由基因C - Myc、DUSP和Cdc25A，控制成纤维细胞增殖。我们使用 MAPK 级联的规范数学模型与随机模型耦合以激活基因调控网络，受不同类型的 FGF 输入（阶跃、二次脉冲、狄拉克增量和白噪声）的影响，以分析基因调控网络对每种类型信号的响应，并确定每种情况下其香农熵值的时间变化。我们的模型表明，细胞周期进程需要 FGFR 通信通道的持续激活，FGF > 1 nM 的步长，并且在 G1/S 过渡期间，GRN 的不确定性保持在大约 2.75 位的稳定值, 表明虽然用 FGF 刺激成纤维细胞继续 G1/S 过渡，但不需要在发射器和基因调控网络之间完成额外的信息交换。我们还发现 FGF 的低频脉冲或低频噪声都具有f ≤ 2.77 Hz，不被 MAPK 级联过滤，可以修改通信通道的输出，即效应蛋白 c-myc、cdc25A 和 DUSP 的数量。我们的模型提出的另一个影响是低频周期性信号和噪声可能会阻塞细胞周期进程，因为 G1/S 转换的 cdc25A 阈值浓度在该过程持续的 10 小时内在细胞核中没有持续. 最后，根据我们的模型，我们可以以 0.96 位/分钟的速度估算该通信信道的容量。