Method for observing kinase function in cells could speed drug discovery

Stanford bioengineers have invented a way to observe and report on the behavior of family of signaling proteins as they go about their crucial work inside living cells.

Think of the human body as an intricate machine whose working parts are proteins: molecules that change shape to enable our organs and tissues to perform tasks such as breathing or eating or thinking.

Of the millions of protein types, 500 in the kinase family are particularly important to drug discovery. Kinases are messengers: They deliver signals that regulate and orchestrate the actions of other proteins. Proper kinase activity maintains health. Irregular activity is linked to cancer and other diseases. For this reason, many drugs seek either to boost or suppress kinase activity.

Now Stanford bioengineers have invented a way to observe and report on the behavior of these signaling proteins as they go about their crucial work inside living cells.

“We’ve been able to observe multiple kinases functioning in living cells, which is something no one else has ever seen,” said Markus Covert, PhD, an assistant professor of bioengineering and senior author of a paper, published online June 19th in Cell, that describes the findings.

“Cancers can occur when a kinase inappropriately tells a cell to ‘grow, grow, grow,’” Covert said. “The reverse can also be true, if a cell reaches what should be the end of its normal life span but the kinase never says ‘die, die, die.’”

Using the new technique, researchers could observe and compare kinase activity in healthy versus diseased cells, then introduce an experimental drug to see how it affects the living cell.

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