The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Rapid and sustained nuclear–cytoplasmic ERK oscillations induced by epidermal growth factor
Open accessAbstract
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.
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Cites
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
Roberts, P. J., & Der, C. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210422 · Cited by 2,788
Oscillations in NF-κB Signaling Control the Dynamics of Gene Expression
Nelson, D. E., Ihekwaba, A. E. C., Elliott, M., Johnson, J. R., Gibney, C. A., Foreman, B. E., Nelson, G., See, V., Horton, C. A., Spiller, D. G., et al. (2004) · Science · doi:10.1126/science.1099962 · Cited by 1,186
Ultrasensitivity in the mitogen-activated protein kinase cascade.
Huang, C. Y., & Ferrell, J. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.19.10078 · Cited by 1,186
A positive-feedback-based bistable ‘memory module’ that governs a cell fate decision.
Xiong, W., & Ferrell, J. E. (2003) · Nature · doi:10.1038/nature02089 · Cited by 741
From in vivo to in silico biology and back
Di Ventura, B., Lemerle, C., Michalodimitrakis, K., & Serrano, L. (2006) · Nature · doi:10.1038/nature05127 · Cited by 290
Cited by
Raf Family Kinases: Old Dogs Have Learned New Tricks
Matallanas, D., Birtwistle, M., Romano, D., Zebisch, A., Rauch, J., von Kriegsheim, A., & Kolch, W. (2011) · Genes & Cancer · doi:10.1177/1947601911407323 · Cited by 386
Surviving apoptosis: life–death signaling in single cells
Flusberg, D. A., & Sorger, P. K. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.03.003 · Cited by 149
Relaxation oscillations and hierarchy of feedbacks in MAPK signaling
Kochańczyk, M., Kocieniewski, P., Kozłowska, E., Jaruszewicz-Błońska, J., Sparta, B., Pargett, M., Albeck, J. G., Hlavacek, W. S., & Lipniacki, T. (2017) · Scientific Reports · doi:10.1038/srep38244 · Cited by 59
Optogenetic actuator – ERK biosensor circuits identify MAPK network nodes that shape ERK dynamics
Dessauges, C., Mikelson, J., Dobrzyński, M., Jacques, M., Frismantiene, A., Gagliardi, P. A., Khammash, M., & Pertz, O. (2022) · Molecular Systems Biology · doi:10.15252/msb.202110670 · Cited by 48
Zhao, W., Yuan, W., Dong, T., Qi, W., Feng, Z., Li, C., & Sun, Y. (2025) · Communications Biology · doi:10.1038/s42003-025-08160-2 · Cited by 16
Metadata
- Authors
- Shankaran, H., Ippolito, D. L., Chrisler, W. B., Resat, H., Bollinger, N., Opresko, L. K., & Wiley, H. S.
- Venue
- Molecular Systems Biology
- Published
- 2009-01
- Volume
- 5
- Issue
- 1
- Pages
- 332-332
- ISSN
- 1744-4292 (ISSN-L)
- OpenAlex
- W2142362541
- Cited by
- 235
- References
- 5
- FWCI
- 7.56
- Type
- journal article
- Language
- en
- Open access
- gold
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- Shankaran, H., Ippolito, D. L., Chrisler, W. B., Resat, H., Bollinger, N., Opresko, L. K., & Wiley, H. S. (2009). Rapid and sustained nuclear–cytoplasmic ERK oscillations induced by epidermal growth factor. Molecular Systems Biology. https://doi.org/10.1038/msb.2009.90
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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