DEC 13, 2016 7:41 PM PST

Protein Engineering Tool Gives Scientists Control of Kinases

WRITTEN BY: Carmen Leitch

Organisms depend on chemical cascades to perform the many life-sustaining functions of cells. Those cascades depend on protein kinases, special enzymes that function to remove one molecule of phosphate from a major source of energy, adenosine triphosphate or ATP, and then donate that molecule to a wide variety of other enzymes and proteins. That energy transfer is a crucial step in many different cellular mechanisms and is vital. While scientists have long been able to activate kinases, there has not been a good way to turn them off, until now. Reporting in the Proceedings of the National Academy of Sciences, scientists have demonstrated that they could control whether a particular kinase was active or not, and for how long. A video from their work illustrating activation and inactivation is shown below.

The study of cellular processes has been impeded because specific kinases that are under study only turn on briefly, explained Andrei Karginov, an Assistant Professor of Pharmacology with the University of Illinois at Chicago College of Medicine.

"Previously, we had the ability to artificially turn on a kinase, but we didn't know how to turn it off, so what we could see was only the result of that kinase being on for a long time." Such an approach has indeed been good for studying how some kinases might contribute to the development of cancer, Karginov said. "But, in living cells, kinases are often turned only for a set period of time, and the duration of this activation often dictates what will happen to the cell. To mimic this transient action we had come up with a new strategy," he concluded.

Two protein-engineering methods were utilized by the research team in order to activate and inactivate one kinase, tyrosine kinase c-Src, a method the researchers say is broadly applicable. By manipulating the activation state of the enzyme for a variety of time periods, the scientists were able to detect a series of structural changes. At first, the cell appeared to change size, first expanding and then contracting – changes driven by the kinase turning on and off. The researchers also were interested to find that a second expansion would sometimes occur after the kinase had been inactivated, an effect that was dependent upon how long it had been turned on for.

Their work has shown that short-term kinase activation is able to exert an effect on a cell. Hopefully the research will also aid other researchers investigating the actions of kinases in the body. Above, another video from their work showing how kinase inactivation can disrupt protein localization, is shown.

If you’d like to know more about the importance of kinases and phosphorylation, check out the following video.

Sources: ScienceDaily via UIC, PNAS

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