Retroactive Signaling in Short Signaling Pathways

Jacques-Alexandre Sepulchre,Sofía D Merajver,Alejandra C Ventura

doi:10.1371/journal.pone.0040806

Abstract

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.

Highlights

One of the most vital processes in biology is the transduction of signals along biochemical pathways, enabling the living cell to elicit appropriate responses to chemical and physical stimuli [1]
We will focus most of our studies on what happens to the upstream cycle in a 2-cycle system, when control parameters of the downstream cycle are modified, as for instance its total available protein or its total phosphatase
In the simplest scheme of a cascade of two covalent modification cycles, the input signal typically is a steep increase of the enzyme modifying the first protein

Summary

Introduction

One of the most vital processes in biology is the transduction of signals along biochemical pathways, enabling the living cell to elicit appropriate responses to chemical and physical stimuli [1]. In this context, the concept of signaling cascade is used as a paradigm or a model of signaling pathways. The concept of signaling cascade is used as a paradigm or a model of signaling pathways It consists of a chain of enzymatic reactions wherein a protein is interconverted reversibly between two forms. The concept of cascade clearly indicates a notion of flow oriented unidirectionally

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Conclusion