Using special techniques to visualize whether the proteins had interacted with the MAPK enzyme, the team found that the relative amount of the first protein controlled how much enzyme was available to interact with the second protein. For example, in the portion of the embryo that would become the head, where the concentration of the first protein was high, much less enzyme was available to act on the second protein than at the other end of the embryo, where the tail would ultimately develop.
"This competition makes sure that the same enzyme signals are interpreted differently in the head and in the tail, thereby allowing for the integration of multiple signals," Shvartsman said.
Based on how the enzyme interacted with the proteins in the head region of the embryo, the team predicted that a third protein also might be competing for the MAPK enzyme in that area. To test the hypothesis, research team members at the Institute for Medical Research Israel-Canada at Hebrew University in Jerusalem used a series of experimental techniques to verify that their proposed protein could bind to the enzyme, an ability that was previously unknown. These findings suggest that the competition model may provide a novel way to identify proteins that are involved in signaling pathways.
Beyond advancing the fundamental understanding of mechanisms that control embryonic patterning, the work has implications for how to target cancer cells, which often exhibit hyperactive MAPK signaling.
"According to our substrate competition idea, MAPK signaling activity directed toward any given substrate decreases when you introduce a competing substrate," Kim said. "In theory, you can lower the activity of MAPK if you introduce a protein whose sole function is to bind to MAPK and thus act as a competitive inhibitor of MAPK signaling to all other substrates." This strategy might one day allow scientists to slow or stop MAPK signaling
|Contact: Kitta MacPherson|