Strong negative feedback from Erk to Raf confers robustness to MAPK signalling
24.05.2011
Fritsche-Guenther R, Witzel F, Sieber A, Herr R, Schmidt N, Braun S, Brummer T, Sers C, Blüthgen N
Mol Sys Biol 2011; 7:489
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. Although a multitude of mechanisms exist that may provide robustness against fluctuating protein levels, we found
that one single feedback from Erk to Raf-1 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.
