The Mammalian MAPK/ERK Pathway Exhibits Properties of a
Negative Feedback Amplifier

Oliver E. Sturm, Richard Orton, Joan Grindlay, Marc Birtwistle, Vladislav Vyshemirsky, David Gilbert, Muffy Calder, Andrew Pitt, Boris Kholodenko, Walter Kolch*

*To whom correspondence should be addressed. E-mail: walter.kolch{at}ucd.ie

This PDF file includes:

• Section 1. Models and modeling.
• Section 2. Model parameters.
• Section 3. SBML files of the models.
• References
• Fig. S1. Absolute concentrations of Raf-1, MEK, and ERK in COS1 and NIH 3T3 cells.
• Fig. S2. Schematic topologies of the models used.
• Fig. S3. Schematic of Raf-1 and the Raf-1 mutants used to probe the NFA hypothesis.
• Fig. S4. Expression of Flag-tagged Raf-1 and the Raf6A mutant.
• Fig. S5. The effects of U0126 on steady-state ppERK abundance with protein concentrations of COS1 cells.
• Fig. S6. The NFA effect also stabilizes non-steady-state dynamic systems.
• Fig. S7. Dose-dependent ERK activation by different stimuli.
• Fig. S8. B-Raf kinase activity is not feedback-inhibited by ERK.
  

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Other Supplementary Material for this manuscript includes the following:

• Tables S1 to S3. Model parameters (Microsoft Excel format). 48 KB
• SBML files of the models (.xml format). 7 KB
  

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