DURHAM, N.C. -- Two critical molecular on and off switches that govern cell processes are intricately bound together in a single control unit, cancer pharmacologists at Vanderbilt University School of Medicine and the Duke University Medical Center have reported.

Their finding, like discovering that the accelerator and brakes of a car are mounted together, represents an important basic insight into the machinery that controls living cells. The discovery also offers the potential for a new strategy for developing drugs that would manipulate one or both of the linked switches to kill cancer cells or bacteria that invade the body, or to exert therapeutic control over cells.

In the May 22 issue of Science, the researchers reported discovering that the linkage of an enzyme called a kinase -- which turns on cell processes by chemically adding a phosphate to another protein -- itself is regulated by another enzyme called a phosphatase that is attached to it. Phosphatases are enzymes that remove phosphates from other enzymes.

Thus, the scientists found that the kinase, called "Calcium-calmodulin dependent protein kinase IV" (CaMKIV) would continue to stimulate cell activity uncontrolled, except that it is quickly shut down by the attached phosphatase, called "Protein Phosphatase 2A" (PP2A).

Reporting the discovery were Ryan Westphal and Brian Wadzinsky of the Vanderbilt department of pharmacology, and Anthony Means and Kristin Anderson of the Duke department of pharmacology and cancer biology. Their research is sponsored by the National Institutes of Health, the Keck Foundation, and the Vanderbilt Diabetes Research and Training Center, Cancer Center and Center for Molecular Neuroscience.

"It's long been known that many cell reactions are driven by phosphorylation by kinases," Means said. "And there's a large amount of evidence that kinase activity is tightly re
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Contact: Dennis Meredith
Dennis@dukenews.duke.edu
(919) 681-8054
Duke University
1-Jul-1998