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Living cell signal discovery boon for cancer treatment

New York: A breakthrough discovery into how living cells process and respond to chemical information could help advance the development of treatment for cancers and other cellular disorders resistant to therapy, a research indicates.

To achieve this, scientists have unlocked the secret behind the activation of the Ras family of proteins - one of the most important components of cellular signaling networks in biology and major drivers of cancers that are among the most difficult to treat. 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.

"We were able to perform single molecule studies of Ras activation in a membrane environment and discover a surprising new mechanism though which Ras signaling is activated by Son of Sevenless (SOS) proteins," said Jay Groves, a chemist with Lawrence Berkeley National Laboratory's (Berkeley Lab) physical biosciences division. The cellular signaling networks of living cells start with receptor proteins residing on a cell's surface that detect and interact with the environment.

Signals from these receptors are transmitted to chemical networks within the cell that process the incoming information, make decisions and direct subsequent cellular activities. For cellular signaling networks involving large numbers of protein molecules, the outcome can be directly determined by the process of averaging. "Our study showed that, in fact, an important aspect of the SOS signal that activates Ras is encoded in the noise," Groves said.

"The protein's dynamic fluctuations between different states of activity transmit information, which means we have found a regulatory coupling in a protein signaling reaction that is entirely based on dynamics, without any trace of the signal being seen in the average behaviour," he said.

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