Computational prediction and analysis of impact of the cross‐talks between JNK and P38 kinase cascades

Signal transduction is a complex protein signaling process with a rich network of multifunctional interactions that occur in a non-linear fashion. Mitogen-activated protein kinase (MAPK) signal transduction pathways regulate diverse cellular processes ranging from proliferation and differentiation to apoptosis. In mammals, out of five, there are three well characterized subfamilies of MAPKs - ERKs (Extracellular signal-regulated kinases), JNKs (c-Jun N-terminal kinases), and P38 kinases, and their activators, are implicated in human diseases and are targets for drug development. Kinase cascades in MAPK pathways mediate the sensing and processing of stimuli. To understand how cells makes decisions, the dynamic interactions of components of signaling cascades are important rather than just creating static maps. Based on enzyme kinetic reactions, we have developed a mathematical model to analyze the impact of the cross-talks between JNK and P38 kinase cascades. Cross-talks between JNK and P38 kinase cascades influence the activities of P38 kinases. Responses of the signals should be studied for network of kinase cascades by considering cross-talks.