LIGHT TURNS ON CAGED ENZYME BIOLOGY: Illuminating a kinase bearing unnatural lysine reveals cell-signaling cascade
A
N UNNATURAL amino acid has given research-
ers a switch to turn on a specific enzyme with light. This tool will allow scientists to determine the timing of cellular signaling and identify which parts of a signaling network might be good drug targets. When organisms or cells receive signals from their surroundings, a cascade of enzymes known as kinases pass those signals along. Each kinase phosphorylates the next one in the chain, until the last one in line receives the signal to perform the desired function. These signaling cascades are complicated networks that can be hard to interpret in real time. Jason W. Chin and Arnaud Gautier of the Medical Research Council Laboratory of Molecular Biology, in Cambridge, England, and Alexander Deiters of North Carolina State University may have found a way to make such interpretation easier by uncoupling a kinase in the middle of the cascade from its usual upstream signals (J. Am. Chem. Soc., DOI: 10.1021/ja1109979). They do this by adding a previously reported unnatural photocaged lysine to the portion of the kinase where its phosphate source, adenosine triphosphate (ATP), binds (J. Am. Chem. Soc., DOI: 10.1021/ja910688s). This unnatural lysine keeps the kinase shut down until light removes the photocaging group to reveal normal lysine, thereby turning on the kinase. In addition, the researchers alter the kinase so that it doesn’t need its usual inputs. By so doing, they transform a kinase that would normally be in the middle of a signaling net-
work into one that’s on the top of its own network. Chin and coworkers use the enzyme MEK1 as a model system. This kinase is in the middle of a signaling pathway that controls a variety of responses to external stimuli, includON SWITCH ing cell proliferation. Shining light on Light removes the protecting cells containing a photocaged MEK1 group (green and red) from removes the photocage and turns on a photocaged lysine (yellow) the phosphorylation of its downstream in the kinase MEK1 (top) and kinases within a minute of illumination. reveals the normal enzyme. Adjusting the illumination time modulates the amount of phosphorylation. Although Chin and coworkers have demonstrated only one model system, Chin expects that the technique will be general because the same lysine is found in the ATP-binding site of nearly all kinases. “We’ve done this for one kinase in the middle, but obviously we could do it for every kinase in the cascade and get information about every elementary step,” Chin says. “We put that together and we’ve got a quantitative model of the whole cascade.” Compared with other methods of taking control of individual kinases in a signaling cascade, Chin’s method is rapid and specifically activates, rather than inhibits, a single targeted kinase. Dario R. Alessi, a researcher in the MRC Protein Phosphorylation Unit at the University of Dundee, in Scotland, says Chin’s “technology could be deployed to regulate the activation of any kinase almost instantaneously by light.” The challenge, he says, “will be to think of how this technology could be used to solve a significant problem in signal transduction.”—CELIA ARNAUD
CORPORATE ESPIONAGE Former Dow employee is found guilty of stealing trade secrets Closing a case that is more than a decade old, a federal jury in Baton Rouge, La., has convicted Dow Chemical researcher Wen Chyu Liu, also known as David W. Liou, of stealing trade secrets and selling them to Chinese firms. Liu, 74, worked for Dow from 1965 until his retirement in 1992. Prosecutors said during the trial that after retirement he conspired with current and former Dow employees at the firm’s Plaquemine, La., and Stade, Germany, sites to steal trade secrets pertaining to the elastomer chlorinated polyethylene. Liu also traveled extensively in China
to market plant process designs, prosecutors allege, and even went so far as to bribe a Dow employee with $50,000 for access to a process manual. Sentencing has not yet been scheduled. Liu faces 10 years in prison for conspiracy to commit trade-secret theft and five years for perjury. “American industries thrive on innovation, and they invest substantial resources in developing new products and technology,” Assistant Attorney General Lanny A. Breuer says. “We will not allow individuals to steal the technology and products that U.S. companies have invested years of
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time and considerable money to create.” Dow closed its Plaquemine chlorinated polyethylene plant in 2009 but continues to operate in Germany. Dow’s major rival is the Chinese firm Yaxing Chemical. To establish its presence, Yaxing bought a plant from Hoechst in Knapsack, Germany; dismantled it; and reassembled it in China about 20 years ago. The Liu trial isn’t the only trade-secret case related to Dow. Last July, the FBI arrested Ke-xue Huang, a 45-year-old exDow AgroSciences researcher, on counts of theft of trade secrets and foreign transportation of stolen property.—ALEX TULLO
J. AM. CHEM. SOC.
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