Extracellular-regulated kinase-mitogen-activated protein kinase cascade: unsolved issues.

This review point out several aspects regarding the mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (Erk) network, which are still pending issues in the understanding how this pathway integrate information to drive cell fates. Focusing on the role of Erk during cell cycle, it has to be underlined that Erk downstream effectors, which are required for mitosis progression and contribute to aneuploidy during tumorigenesis, remain to be determined. In addition to the identity of the terminal enzymes or effectors of Erk, it has to be stressed that the dynamic nature of the Erk signal is itself a key factor in cell phenotype decisions. Development of biophotonics strategies for monitoring the Erk network at the spatiotemporal level in living cells, as well as computational and hypothesis-driven approaches, are called to unravel the principles by which signaling networks create biochemical and biological specificities. Finally, Erk dynamics might also be impacted by other post-translational modification than phosphorylation, such as O-GlcNAcylation.