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New discovery in living cell signaling
Date:7/3/2014

dynamic transitions of individual molecules encoded information that is lost in the average."

What the collaboration discovered is that SOS regulation is based on the dynamics of distinct stochastic fluctuations between different activity states that last approximately 100 seconds but do not show up in ensemble averages. These long-lived fluctuations provide the mechanism of allosteric SOS regulation and Ras activation.

"The allosteric regulation of SOS deduced from cell biological and bulk biochemical studies is conspicuously absent in direct single molecule studies," Groves says. "This means that something that was inferred to exist proved to be missing when we did an experiment that explicitly measured it. The dynamic fluctuations we observed within the system correlated with the expected allosteric regulation, and subsequent theoretical modeling confirmed that such stochastic fluctuations can give rise to known bulk effects."

Understanding the role of stochastic dynamic fluctuations as signaling transduction mechanisms for Ras proteins, could point the way to new and effective therapies for Ras-driven cancers and other cellular disorders. In their Science paper, the collaborators also express their belief that the dynamic fluctuations mechanism they discovered is not unique to Ras proteins but could be applicable to a broad range of other cellular signaling proteins.

"The reason this mechanism has not been reported before is that no previous experiment could have revealed it," Groves says. "All previous experiments on this system - and most others for that matter - were based on average behavior. Only single molecule measurements that can look at all the molecules in the system are capable of revealing this type of effect, which we think may prove to be very important in the function of living cell signaling systems."


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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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