title: Strong negative feedback from Erk to Raf confers robustness to MAPK signalling.
abstract: 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.
authors: Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Raphaela
authors: R
authors: Fritsche-Guenther
authors: Franziska
authors: F
authors: Witzel
authors: Anja
authors: A
authors: Sieber
authors: Ricarda
authors: R
authors: Herr
authors: Nadine
authors: N
authors: Schmidt
authors: Sandra
authors: S
authors: Braun
authors: Tilman
authors: T
authors: Brummer
authors: Christine
authors: C
authors: Sers
authors: Nils
authors: N
authors: Blüthgen
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