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Rising expectations from new yeast study

ever we get a wound, immune cells detect the source of chemical signals coming from the wound and migrate toward it. Chemotropism is also relevant to cancer because tumor cells metastasize in response to chemical signals released by specific tissues."

At the molecular level, the yeast mating response works through a series of steps: the signaling pheromone binds to a receptor on the cell membrane, thus activating a signaling molecule called a G-protein. G-protein is made of two parts, G-alpha and G-beta-gamma. G-beta-gamma triggers a sequence of signals along a pathway of enzymes, ending in the activation of a protein called a MAPK, which enters the cell nucleus and affects targets that block cell division.

To resume division, the cells must turn off the mating signal. Exactly how this worked was unclear until Metodiev and Stone, using a research technique called proteomics, discovered that the other part of the G-protein (G-alpha) eventually bypasses this linear signal progression and binds directly to the bottom-level MAPK. It then diverts the MAPK from the nucleus, which allows the growth signal to turn back on. This G-alpha/MAPK binding was previously unknown.

The UIC scientists also discovered that G-alpha lures the MAPK enzymes to the cell's plasma membrane where it works to help orient cell growth toward another cell's chemical signal.

"In contrast to traditional therapies, today's modern drug discovery process is directed at specific proteins and protein-protein interactions," said Metodiev. "In this case, we have demonstrated the interaction of two very important and well-characterized signaling molecules, G-alpha and MAPK. This interaction is a natural target of drug discovery research."

"It's basic scientific research but definitely has the potential to influence therapeutics," said Stone. "There are many human diseases related to problems in controlling cell growth and differentiation. For example, if we know
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Contact: Paul Francuch
francuch@uic.edu
312-996-3457
University of Illinois at Chicago
23-May-2002


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