Cross-regulation between CDK and MAPK control cellular fate

Background: Commitment to a new cell cycle is controlled by a number of cellular signals. Mitogen-activated protein kinase (MAPK) pathways, which transduce multiple extracellular cues, have been shown to be interconnected with the cell cycle and can modulate its progression. Methods: In budding yeast, we have introduced fluorescent biosensors that monitor in real time the signaling activity of the MAPKs Fus3 and Kss1 and the cyclin-dependent kinase (CDK) in individual cells. We have quantified in hundreds of live single cells the interplay between the MAPKs regulating the mating response and the CDK controlling cell cycle progression. Results: Different patterns of MAPK activity dynamics could be identified by clustering cells based on their CDK activity, denoting the tight relationship between these two cellular signals. Our data suggest that beyond the already well-established mechanisms of regulation between the MAPK and the CDK, additional mechanisms remain to be identified. Conclusion: A tight interplay between MAPK pathways and the cell cycle is essential to control cellular proliferation and cell fate decisions.