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Oscillating Signaling Protein Helps Create Predictive Models
Integrating theory and experiment provides insights to ERK's link to disease
Enlarge Image. Change in ERK distributon after EGF addition. Cells expressing a green fluorescence ERK and a red fluorescence marker of the cytoplasm were treated with EGF for the time indicated at the top. Top panels are the original fused images. Bottom panels are the ratio of ERK:cytoplasm intensity. This shows that ERK is selectively concentrated in the nucleus in a periodic manner.
For the first time, scientists have proven that a vital protein controlling cellular proliferation, ERK, oscillates in and out of the nucleus of human breast cells. Researchers from Pacific Northwest National Laboratory and led by EMSL Lead Scientist for Biology, Steve Wiley, observed sustained oscillations of ERK between the nucleus and cytoplasm. By integrating multiple scientific disciplines, instruments, and standard computational packages at the Department of Energy's EMSL, the team proved the long-suspected oscillations. Each cycle took approximately 15 minutes. The oscillations were persistent, with more than 45 cycles observed. The oscillations were also independent of the phase of the cell. With the quantitative data from this study, modeling experts can constrain mathematical models to obtain more accurate simulations and obtain better behavioral predictions of ERK activity. See the video [movie, 2MB].
This research was published in Molecular Systems Biology and quickly became the top download on the journal's website in December 2009.
Scientific impact: Although the ERK pathway has a central role in how cells respond to growth factors, its regulatory structure and dynamics are not completely understood. This characterization of single-cell ERK dynamics provides experimentally backed constraints for modeling the regulatory structure of the signaling cascade and other behaviors. This research is part of EMSL's ongoing efforts in predicting biological functions from molecular and chemical data.
Societal impact: Understanding ERK's role in regulating cell proliferation is vital to research designing antiproliferative drugs to treat cancer and other diseases.
For more information: Contact EMSL Communications Manager Mary Ann Showalter (509-371-6017).
Reference: Shankaran H, DL Ippolito, WB Chrisler, H Resat, N Bollinger, LK Opresko, and HS Wiley. 2009. "Rapid and Sustained Nuclear-Cytoplasmic ERK Oscillations Induced by Epidermal Growth Factor." Molecular Systems Biology 5(322), doi:10.1038/msb.2009.90
Acknowledgments: The research was funded by Pacific Northwest National Laboratory's Biomolecular Systems Initiative and the National Institutes of Health.
Learn more about this and other biological research being conducted by scientists in PNNL's Biological Sciences Division.