Mechanisms Conferring Robustness to Erk1/2 Signalling

On the molecular scale even clonal cells do not look alike, as gene expression is inherently stochastic and in consequence protein levels fluctuate. Cellular signal transduction pathways are affected by this gene expression noise, as proteins relay information about the environment to the nucleus, ultimately regulating cell fate decisions. So how can signalling work in a reliable and reproducible fashion? A combination of experiments and mathematical modelling reveals how negative feedbacks and phosphorylation cycles create the remarkable robustness of MAPK signalling when the concentration of Erk1/2 is increased or reduced by targeted perturbations.