Signal transduction meets systems biology: deciphering specificity determinants for protein-protein interactions.

SUMMARY: Two recent papers (Gao et al. 2008 and Skerker et al. 2008) describe investigations into the specificity of protein-protein interactions that occur during signal transduction by two-component regulatory systems. This MicroCommentary summarizes and provides context for the reported findings. The results offer insights into molecular determinants that provide specificity to maintain signal separation and thus prevent deleterious cross-talk between pathways, as well as the potential extent and nature of interactions that may combine signals to achieve beneficial cross-regulation among pathways. The methods employed are suitable for application to other systems.