Splitting up kinases
February 26, 2014 § Leave a comment
Researchers have figured out a way to bend kinases at their will. In a paper recently published in the Journal of the American Chemical Society, Indraneel Ghosh and colleagues at the University of Arizona describe engineering these enzymes, which are critical for signaling pathways, so that they can be controlled by researchers. These engineered kinases should “allow for a more precise understanding of signaling cascades that are currently unavailable,” says Ghosh.
Scientists have been interested in manipulating enzymes with exquisite precision because the manipulation helps them to understand how these molecular machines work. Kinases also represent a lucrative class for drug targets because many of them have been identified to be involved in disease conditions, such as cancer. Knowing how kinases work in detail helps to develop highly targeted drugs.
Ghosh and colleagues demonstrated that one way to turn kinases on and off at will was to split the enzymes into two. They then connected the two parts of the enzyme with a special linker. When given a specific small molecule, such as the immunosuppressant rapamycin, two parts of the split enzyme came together and became activated like their normal counterparts. Because these enzymes could be activated with a small molecule, Ghosh and colleagues called them “ligand inducible split-kinases.”
The researchers showed that the approach could be used on four different kinases, suggesting that the method is broadly applicable. Ghosh says the long-term goal of the project is to have multiple ligand inducible split-kinases within a cell so that researchers can understand how these enzymes work relative to one another in the complex network of signaling pathways.