Challenges ahead in signal transduction: MAPK as an example

Signal transduction is the process of converting one kind of signal or stimulus into another, with the goal of processing external or internal signals into diverse functions. In recent years, progress has been made in identifying signaling pathways, investigating cross-talk and feedbacks in signaling modules, analyzing cell-type specific signaling, and unraveling spatial-temporal aspects, such as receptor clustering into micro-domains, dynamic localization, and mathematical modeling. Here, we used the receptor/MAPK signaling system as an example, and we discuss the current and remaining challenges: the role of scaffolds and signaling machines, the importance of concentration and competition, the use of structural information, the integration of large-scale proteomic datasets, and the future challenge of integrating alternative splicing into signaling pathways.