Robustness and Specificity in Signal Transduction via Physiologic Protein Interaction Networks

The collective Protein:Protein Interactions (PPI) of a cell are thought to represent a system with emergent network properties that integrate signals from a multiplicity of inputs into coordinated responses. It is hypothesized that the PPI network supplies both specificity for many distinct signals that utilize common intermediate pathways, and also robustness by allowing specific signals to be communicated by alternate routes. Progress with genetic networks points to these concepts, but the extent to which PPI networks possess these properties has not been empirically tested, due to lack of quantitative data needed for such assessments. Here, a hypothetical physiologic PPI network is used to illustrate how signaling robustness and specificity could be manifest under conditions of (i) deletion mutation, or (ii) changes in signaling due to variation in environmental conditions or stimuli. It is proposed that advances in technology enabling empirical analysis of PPI network principles will have the potential to significantly impact basic understanding of signaling mechanisms, and contribute to the generation of novel applications in drug screening and pharmacology.