SAN FRANCISCO, June 25 (Xinhua) -- Research results from University of Washington (UW) indicates that key cellular communication machinery is more regionally constrained inside the cell than was previously thought.
The findings, reported in the journal Science, overturn long-held views on a basic messaging system within living cells.
Led by John Scott, professor and chair of pharmacology at the UW School of Medicine and his colleague Donelson Smith, the researchers explain that within a cell, the precise positioning of such messaging components allows hormones, the body's chief chemical communicators, to transmit information to exact places inside the cell. And accurate and very local activation of the enzyme under their study helps assure a correct response occurs in the right place and at the right time.
"The inside of a cell is like a crowded city," according to Scott, "It is a place of construction and tearing down, goods being transported and trash being recycled, countless messages, (such as the ones we have discovered), assembly lines flowing, and packages moving. Strategically switching on signaling enzyme islands allows these biochemical activities to keep the cell alive and is important to protect against the onset of chronic diseases such as diabetes, heart disease and certain cancers."
Advances in electron microscopy and native mass spectrometry enabled the researchers to determine that a critical component of the signaling system, anchored protein kinase A, remains intact during activation. Parts of the molecule are flexible, allowing it to both contract and stretch, with floppy arms that can reach out to find appropriate targets. Still, where the molecule performs its act, space is tight. And the distance is about the width of two proteins inside the cell.
"We realize that in designing drugs to reach such targets that they will have to work within very narrow confines," Scott was quoted as saying in a news release.
One of his research group's goals is figuring out how to deliver precision drugs for cancer and other serious diseases to the right address within this teeming cytoplasmic metropolis.
"Insulating the signal so that the drug effect can't happen elsewhere in the cell is an equally important aspect of drug development because it could greatly reduce side effects," Scott said.
The group is collaborating with cancer researchers to better understand the molecular causes and possible future treatments for a certain liver malignancy. This particular liver cancer arises from a mutation that produces an abnormal form of the enzyme that is the topic of this current work, protein kinase A, and alters the enzyme's role in cell signaling.
