BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL2306170002?filename=Model%20of%20nuclear_cytoplasmic%20ERK%20oscillations%20induced%20by%20epidermal%20growth%20factor.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL2306170002?filename=Model%20of%20nuclear_cytoplasmic%20ERK%20oscillations%20induced%20by%20epidermal%20growth%20factor.pyprimaryOK200Yirui ChenNon-curatedordinary differential equation modelL3V1https://www.ebi.ac.uk/biomodels/MODEL230617000219953086falseBioModelsSBMLModelsHarish2009 nuclear–cytoplasmic ERK oscillation model2009MODEL2306170002Harish Shankaran, Danielle L Ippolito, William B Chrisler, Haluk Resat, Nikki Bollinger, Lee K Opresko, H Steven WileyHarish Shankaran19953086, Although the ERK pathway has a central role in the response of cells to growth factors, its regulatory structure and dynamics are incompletely understood. To investigate ERK activation in real time, we expressed an ERK-GFP fusion protein in human mammary epithelial cells. On EGF stimulation, we observed sustained oscillations of the ERK-GFP fusion protein between the nucleus and cytoplasm with a periodicity of approximately 15 min. The oscillations were persistent (>45 cycles), independent of cell cycle phase, and were highly dependent on cell density, essentially disappearing at confluency. Oscillations occurred even at ligand doses that elicited very low levels of ERK phosphorylation, and could be detected biochemically in both transfected and nontransfected cells. Mathematical modeling revealed that negative feedback from phosphorylated ERK to the cascade input was necessary to match the robustness of the oscillation characteristics observed over a broad range of ligand concentrations. Our characterization of single-cell ERK dynamics provides a quantitative foundation for understanding the regulatory structure of this signaling cascade.. null, 5. Systems Biology Program, Pacific Northwest National Laboratory, Richland, WA, USA.ychen239@uw.eduUniversity of WashingtonAlthough the ERK pathway has a central role in the response of cells to growth factors, its regulatory structure and dynamics are incompletely understood. To investigate ERK activation in real time, we expressed an ERK-GFP fusion protein in human mammary epithelial cells. On EGF stimulation, we observed sustained oscillations of the ERK-GFP fusion protein between the nucleus and cytoplasm with a periodicity of approximately 15 min. The oscillations were persistent (>45 cycles), independent of cell cycle phase, and were highly dependent on cell density, essentially disappearing at confluency. Oscillations occurred even at ligand doses that elicited very low levels of ERK phosphorylation, and could be detected biochemically in both transfected and nontransfected cells. Mathematical modeling revealed that negative feedback from phosphorylated ERK to the cascade input was necessary to match the robustness of the oscillation characteristics observed over a broad range of ligand concentrations. Our characterization of single-cell ERK dynamics provides a quantitative foundation for understanding the regulatory structure of this signaling cascade.Rapid and sustained nuclear-cytoplasmic ERK oscillations induced by epidermal growth factor.Shankaran Harish H, Ippolito Danielle L DL, Chrisler William B WB, Resat Haluk H, Bollinger Nikki N, Opresko Lee K LK, Wiley H Steven HSfalseHarish2009 - nuclear–cytoplasmic ERK oscillation modelThis model is based on the supplementary material of the publication “Rapid and sustained nuclear–cytoplasmic ERK oscillations induced by epidermal growth factor This model is an Antimony version of the original MATLAB model.2023-06-172023-06-192023-06-17MODEL230617000219953086