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New strategy developed to study disease: Reveals insights into cancer and treatment leads

For the first time, Johns Hopkins researchers were able to easily jumpstart the activity of a well-known cancer protein in live cells with a small molecule, a strategy that pinpointed key players in the cancer process and can be used to determine new therapeutic targets. What's more, the scientists' study, published in the March 3 issue of Science, identifies a simple method to further understand the complex mechanisms that underlie cancer as well as other diseases and may provide an easy model to screen for new cancer drugs.

"Our study reveals a new way to study proteins in live cells, in this case, a tyrosine kinase implicated in causing cancer," says the study's lead author, Philip A. Cole, M.D., Ph.D., director of the Department of Pharmacology and Molecular Sciences at The Johns Hopkins University School of Medicine. "This approach helped identify potentially important therapeutic targets and in the future may provide a method to easily screen cancer treatments."

In the study, Cole and his colleagues examined the tyrosine kinase Src (pronounced SARK), a clinically important cancer protein that scientists have heavily studied but do not completely understand. The Johns Hopkins researchers developed a special mutated version of the Src protein and incorporated it into live animal cells. The mutated version was inactive but contained an "ignition switch" that would turn it back on. They determined that the small molecule, imidazole, could act as the key. Imidazole fit into a pocket in the mutated structure of the Src protein, which mended the structure and reinstated Src's activity. Removal of imidazole quickly shut the protein off again.

"This strategy provided a controlled environment to study Src," says Cole. "This helped us uncover some new and unexpected insights into how the cancer protein creates its havoc, as well as new treatment leads." For one, the model provided evidence that Src interacts with CrkL, a signaling protein
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Contact: Eric Vohr
evohr1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
7-Mar-2006


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