Courtney Zahn

Cell Biology Extra Credit

11/26/14
Discovery in the Signaling of Living Cells Ras Activation by SOS
Molecules
Scientists with the U.S. Department of Energy, Lawrence
Berkeley National Laboratory and the University of California, Berkeley,
led an international team of investigators to a new discovery in the
signaling of living cells and Ras activation by SOS molecules. More
specifically, they developed a supported membrane arrangement out
of lipids embedded with metal nanostructures, which allowed for
placement and controlled spacing of proteins and other cellular
molecules on the membranes. The supported membrane allowed the
researchers to collect individual SOS molecules and trap the Ras
molecules once they were activated.
Cell signaling is dependent on the activation of Ras, but the
mechanism is not completely understood. SOS enzymes activate Ras
at cell membranes. So, in order to fully understand the mechanism of
Ras activation, observing single SOS molecules in a membrane
environment during interactions with Ras are necessary. Before their
development of the supported membrane, most knowledge of Ras
signal activation came from bulk assays, in solution, or in live cells,
which did not explain the role of the membrane environment in
signaling. Conclusions were previously based on the average behavior
of the entire group of proteins. The average behavior of identical
proteins in cellular signaling networks that include a lot of proteins is
an acceptable measurement despite the variability of individual
proteins. This is not the case, however, for networks involving only a
small number of proteins.
Averaging the variable behavior of individual SOS molecules
involved in Ras activation is not possible. This is due to the relatively
small number of SOS molecules involved in the activation. Stochastic
noise is the name that was given to this variation in quantities, and it
hindered the knowledge of Ras signal activation by SOS molecules.
The new development of a supported membrane arrangement enabled
the researchers to observe the activity of every single molecule in realtime, which revealed how the dynamic transitions of single molecules
encoded information that was missed when observing the average
behavior of the entire group of proteins.
The researchers found the noise contained important information
regarding the SOS signal that activates Ras. They discovered a
regulatory coupling in a protein reaction that was never before seen
when only observing average behavior. The many cancers (and other
disorders) caused by problems during Ras activation, are untreatable

due to lack of knowledge regarding the mechanism by which the Ras

family of proteins is activated. This discovery in the signaling of living
cells could therefore pave the way for effective treatments for many
resistant cancers and disorders.

References
Yarris, Lynn. (2014). New discovery in living cell signaling Berkeley lab
researchers help find that what was believed to be noise is an
important signaling factor. Berkley Lab. Published online 2014,
July 3. Retrieved from http://newscenter.lbl.gov/2014/07/03/newdiscovery-in-living-cell-signaling/.