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Making Sense of Signal Integration

April 21, 2010

Brewer's yeastAlthough humans and the single-celled budding yeast Saccharomyces cerevisiae are eukaryotes separated by about one billion years on the evolutionary ladder, roughly one-third of the yeast’s 6,000 genes are related to human genes. That is, the human and yeast genes contain stretches of DNA that are close or identical in sequence, suggesting they are essential to life or else they would have been lost during evolution. As scientists have known for years, this means S. cerevisiae has quite a bit to tell them not only about the structure of DNA but how a eukaryotic cell works as an integrated system of biological inputs and outputs.

Scientists already have defined in great biochemical detail many of the fundamental signaling pathways that allow a budding yeast cell to function. Still unanswered, though, is the next logical question of how multiple pathways integrate their signals to prompt a highly coordinated biological response. One of the most studied of these biological responses is the decision of S. cerevisiae to form branched chains of elongated, interconnected filaments when nutrients are limited. Scientists widely regard this growth response as a model for cell differentiation, an issue of great importance throughout biology.

In the March issue of the journal PLoS Genetics, a team of NIDCR-supported scientists provide one of the first answers to the signal integration question. They show that many of the major filamentation regulatory pathways were required to activate the MAPK pathway, the coupling mechanism that relays the inputted signal onward for the appropriate cellular response. The researchers found that the pathways are connected to co-regulatory circuits, which trigger a systemic coordination of the differentiation response. “The ‘top-view’ perspective we obtained has shown that many of the major regulatory proteins that control filamentous growth also control MAPK signaling,” the authors noted. “This finding is challenging to accept given that many of the pathways are currently viewed as separate entities. Nevertheless, this view is consistent with an emerging systems-level appreciation of pathway regulations in complex situations – cell differentiation, stem cell research, and cancer – where pathway interconnectedness drives the rationale for drug development and new therapeutic endeavors.”

  • Multiple Signals Converge on a Differentiation MAPK Pathway. Chavel CA, Dionne HM, Birkaya B, Joshi J, Cullen PJ. PLoS Genet 6(3):e1000883, March 2010.

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This page last updated: February 26, 2014