Cell Signaling in living cell
The information about the cancer development and cellular disorders can be determined by knowing the cellular signaling in which the number of protein molecules is involved. Ras activation in a living cell, however, involves a relatively small number of SOS molecules, making it impossible to average the variable behavior of the individual molecules. Molecular signaling can occur between different organisms, whether unicellular or multicellular, the emitting organism produces the signaling molecule, secrete it into the environment, where it diffuses, and it is sensed or internalized by the receiving organism. Intraspecies signaling occurs especially in bacteria, yeast, social insects, but also in many vertebrates. Ras proteins are essential components of signaling networks that control cellular proliferation, differentiation and survival. Mutations in Ras genes were the first specific genetic alterations linked to human cancers and it is now estimated that nearly a third of all human cancers can be traced to something going wrong with Ras activation. Defective Ras signaling has also been cited as a contributing factor to other diseases, including diabetes and immunological and inflammatory disorders. Ras proteins are anchored play a major role in their activation through SOS exchange factors. SOS activity in turn was believed to be allosterically regulated through protein and membrane interactions, but this was deduced from cell biological studies rather than direct observations. For a better understanding of how Ras activation by SOS is regulated, scientists need to observe individual SOS molecules interacting with Ras in a membrane environment.
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. Proteins but could be applicable to a broad range of other cellular signaling proteins.