
Strong negative feedback from Erk to Raf confers robustness to MAPK signalling
Author(s) -
FritscheGuenther Raphaela,
Witzel Franziska,
Sieber Anja,
Herr Ricarda,
Schmidt Nadine,
Braun Sandra,
Brummer Tilman,
Sers Christine,
Blüthgen Nils
Publication year - 2011
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2011.27
Subject(s) - mapk/erk pathway , robustness (evolution) , biology , microbiology and biotechnology , signalling , signal transduction , kinase , phosphorylation , protein kinase a , genetics , gene
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.