Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/msb.2011.27
Keywords
expression noise; MAPK signalling; negative feedback; Raf; robustness
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Funding
- German Federal Ministry of Education and Research (BMBF)
- German Research Foundation (DFG) [SFB618]
- CRC [850]
- EXC [294 BIOSS]
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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. Molecular Systems Biology 7: 489; published online 24 May 2011; doi: 10.1038/msb.2011.27
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