A kinetic model reconciles observed ERK phosphorylation, localization, and activity responses A Schematic of a simple kinetic model including cytosolic.

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A kinetic model reconciles observed ERK phosphorylation, localization, and activity responses A Schematic of a simple kinetic model including cytosolic and nuclear substrates that bind to and are phosphorylated by active ERK. B–J Means of calculated time courses (solid lines), representing a global ensemble fit to the data, are plotted along with the means of the corresponding experimental  measurements (black circles). A kinetic model reconciles observed ERK phosphorylation, localization, and activity responses A Schematic of a simple kinetic model including cytosolic and nuclear substrates that bind to and are phosphorylated by active ERK. B–J Means of calculated time courses (solid lines), representing a global ensemble fit to the data, are plotted along with the means of the corresponding experimental  measurements (black circles). Broken lines report mean ± s.d. of the model output for all parameter sets in the ensemble (n = 10 000). The data fit for maximal  PDGF stimulation conditions comprises MEK (B) and ERK (C) phosphorylation measured by immunoblotting, mono‐phosphorylated ERK2 [pTEY, (D)] and  diphosphorylated ERK2 (E) measured by mass spectrometry, nuclear localization of ERK (F), and cytosolic (G) and nuclear (H) ERK activities. Also fit were the  experiments in which cytosolic (I) and nuclear (J) ERK activities were monitored in cells maximally stimulated with PDGF followed by MEK inhibition. Data information: In (D), the data for the other mono‐phosphorylated form of ERK2, TEpY, are also shown (red triangles).Source data are available online for this figure. Shoeb Ahmed et al. Mol Syst Biol 2014;10:718 © as stated in the article, figure or figure legend