Systems Biology Ireland, University College Dublin, Belfield, Dublin, Ireland.
Biophys J. 2010 Jul 7;99(1):59-66. doi: 10.1016/j.bpj.2010.04.014.
Multiple cellular proteins are covalently modified (e.g., phosphorylated/dephosphorylated) at several sites, which leads to diverse signaling activities. Here, we consider a signaling cascade that is activated at the plasma membrane and composed of two-site protein modification cycles, and we focus on the radial profile of the concentration landscapes created by different protein forms in the cytoplasm. We show that under proper conditions, the concentrations of modified proteins generate a series of peaks that propagate into the cell interior. Proteins modified at both sites form activity gradients with long plateaus that abruptly decay at successive locations along the path from the membrane to the nucleus. We demonstrate under what conditions signals generated at the membrane stall in the vicinity of that membrane or propagate into the cell. We derive analytical approximations for the main characteristics of the protein concentration profiles and demonstrate what we believe to be a novel steady-state pattern formation mechanism capable of generating precise spatial guidance for diverse cellular processes.
多种细胞蛋白在多个位点发生共价修饰（例如，磷酸化/去磷酸化），从而产生多种信号活性。在这里，我们考虑一种在质膜上激活的信号级联反应，它由两个位点的蛋白修饰循环组成，并且我们专注于不同蛋白形式在细胞质中形成的浓度景观的径向分布。我们表明，在适当的条件下，修饰蛋白的浓度会产生一系列的峰，这些峰会在细胞内部传播。在两个位点都被修饰的蛋白形成带有长平台的活性梯度，该平台会在沿着从膜到核的路径的连续位置上突然衰减。我们证明了在什么条件下，在膜附近产生的信号会停滞在该膜附近或传播到细胞内部。我们推导出蛋白浓度分布的主要特征的解析近似，并展示了我们认为是一种新的稳态模式形成机制，它能够为各种细胞过程生成精确的空间导向。
