Institut Non Linéaire de Nice, UMR 7335 CNRS-University of Nice Sophia Antipolis, Valbonne, France.
PLoS One. 2012;7(7):e40806. doi: 10.1371/journal.pone.0040806. Epub 2012 Jul 26.
In biochemical signaling pathways without explicit feedback connections, the core signal transduction is usually described as a one-way communication, going from upstream to downstream in a feedforward chain or network of covalent modification cycles. In this paper we explore the possibility of a new type of signaling called retroactive signaling, offered by the recently demonstrated property of retroactivity in signaling cascades. The possibility of retroactive signaling is analysed in the simplest case of the stationary states of a bicyclic cascade of signaling cycles. In this case, we work out the conditions for which variables of the upstream cycle are affected by a change of the total amount of protein in the downstream cycle, or by a variation of the phosphatase deactivating the same protein. Particularly, we predict the characteristic ranges of the downstream protein, or of the downstream phosphatase, for which a retroactive effect can be observed on the upstream cycle variables. Next, we extend the possibility of retroactive signaling in short but nonlinear signaling pathways involving a few covalent modification cycles.
在没有明确反馈连接的生化信号通路中，核心信号转导通常被描述为一种单向通讯，在共价修饰循环的前馈链或网络中从上游到下游进行。在本文中，我们探讨了一种称为回溯信号的新信号类型的可能性，这种信号是由最近证明的信号级联中的回溯性提供的。回溯信号的可能性在最简单的情况下进行了分析，即信号循环的双环级联的稳定状态。在这种情况下，我们详细说明了上游循环的变量受到下游循环中蛋白质总量变化或去磷酸化酶使同一蛋白质失活的影响的条件。特别地，我们预测了可以在下游循环变量上观察到回溯效应的下游蛋白质或下游磷酸酶的特征范围。接下来，我们在涉及几个共价修饰循环的短但非线性信号通路中扩展了回溯信号的可能性。
