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Enzyme activation appears key in helping internal clock tell night from day

CHAMPAIGN, Ill. -- Feel like time is repeating itself and won't move on? It could be your internal clock is backpedaling because your PKG-II is out of whack.

That scenario was played out at the University of Illinois at Urbana-Champaign in experiments at a molecular level deep within the brain of rats where, like in all mammals, the primary circadian clock is located. The clock is a dynamic biological process with a near-24-hour cycle. PKG-II is an enzyme, a protein that triggers biochemical reactions.

Reporting in the Aug. 19 issue of the journal Neuron, the Illinois scientists say that the activation of PKG-II may be the critical control point that tells our biological clock to proceed by putting night behind and journeying into a new day.

In their research, the scientists blocked the phosphorylation action of PKG-II during the normal cycling of the clock. By doing so, they disrupted the key activity of this kinase enzyme that adds phosphates to proteins, a signaling mechanism necessary for information transfer in cells.

The internal clock produces the 24-hour rhythm in the brain and all cells. The cycle consists of an automatically regulated loop of transcription and translation of special clock genes, whose products act as "gears" of the clockwork. Correct cycling is vital to the oscillation of metabolism and behaviors, which happen during sleep and wakefulness.

"Without PKG-II, the clock behaves as if locked in a dynamic loop that encompasses the biochemical state of late night," the researchers wrote. "By potentially interacting with CLOCK (a critical protein of the central clockwork) during its phosphorylation, PKG-II may influence core clock components to signal the completion of nighttime processes and permit transit to the daytime domain. Thus, clock-controlled activation of PKG-II may serve as a critical checkpoint of temporal state at the night-to-day transition, which would align with dawn in the solar cycl
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Contact: Jim Barlow, Life Sciences Editor
jebarlow@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
18-Aug-2004


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