Complexity in signal transduction

This review is focused on complexity in cell signaling. Signaling experiments have demonstrated that many different stimuli activate the same signaling pathways yet result in different outcomes. Differences in the cellular machinery between cells explain response variation between cell types, but for a single cell type an appealing explanation is still lacking. The kinetic disconnect between cell signal transduction and a cellular action is highlighted; possible explanations for this disconnect, such as a series of cascading autocrine signaling molecules and new research suggesting that cells experience multiple rounds of reactivation in numerous cell signaling pathways, are reviewed. Additionally, evidence that kinase pathways exhibit frequency and amplitude modulation is examined. From this review, a new model of signal transduction is proposed whereby multiple signal transduction pathways are reactivated over time to orchestrate unique outcomes in physiological processes.