Round and Round
The meaning of the handful of oscillations found by researchers within cells has been controversial. Calcium levels cycle up and down in nerve cells, but scientists still debate why 20 years after the discovery. The production and destruction of the well-known cancer-related protein p53 continuously cycles, but its purpose is unclear. ERK is one protein in a long chain of command involved in cell growth. Because ERK gets repeatedly activated and deactivated by various proteins, Wiley and colleagues thought it might oscillate.
ERK has a role in human breast tissue, where the molecule epidermal growth factor, or EGF, sends a message from the cell surface to the rest of the cell in a carefully regulated manner that includes ERK. In breast cancer, that chain of command goes awry and cells grow out of control. Cancer drug researchers target players in the chain of command to control that growth.
For that reason, Wiley and his colleagues wanted to better understand EGF's chain of command, also known as its signaling pathway. Most researchers use cancer cells, which are easy to manipulate in culture, but Wiley studied healthy breast tissue to find out what goes on in normal cells. In addition, most research examines the population of cells on average, in which individual differences between cells can get lost. This work watched single cells.
Researchers know a lot about what activates ERK and what shuts it down in the EGF signaling pathway. To follow ERK, the scientists engineered healthy, cultured breast cells to produce a green-glowing version of the protein. When EGF turns on the signaling pathway, the team verified that the green version of ERK is activated in the same way as the regular version is, by the addition of a chemical group. Other proteins deactivate ERK by removing the chem
|Contact: Mary Beckman|
DOE/Pacific Northwest National Laboratory