Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Robustness of MAPK signalling at various expression levels of Erk1/2
Franziska Witzel, Raphaela Fritsche-Guenther, Anja Sieber, Ricarda Herr, Nadine Schmidt, Sandra Braun, Tilman Brummer, Christine Sers, Nil Blütghen

Last modified: 2014-06-09


Protein levels within signal transduction pathways vary strongly from cell to cell. Here we analysed how signalling pathways can still process information quantitatively despite strong heterogeneity in protein levels. We systematically perturbed the protein levels of Erk, the terminal kinase in the MAPK signalling pathway in a panel of human cell lines. We found that the steady-state phosphorylation of Erk is very robust against perturbations of Erk protein level. Several mechanisms might act to establish robustness. They could be of purely kinetic nature, i.e. a consequence of the way Erk is activated. Another reasonable explanation might be the action of post-translational or transcriptional feedbacks. We have tested these hypotheses theoretically and experimentally and found that one single feedback from Erk to c-Raf accounts for the observed robustness. Surprisingly, robustness is provided through a fast post-translational mechanism although variation of Erk levels occurs on a timescale of days.