Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Advanced X-ray, neutron beam imaging reveal workings of powerful biochemical switch PKA

10.10.2014

A University of Utah-led study using X-rays and neutron beams has revealed the inner workings of a master switch that regulates basic cellular functions, but that also, when mutated, contributes to cancer, cardiovascular disease and other deadly disorders.

Learning more about how the Protein Kinase A (PKA) switch works will help researchers to understand cellular function and disease, according to Donald K. Blumenthal, Ph.D., associate professor of pharmacology and toxicology at the University of Utah (U of U) College of Pharmacy who led the study. "To develop new drugs and treatments for disease, it's important to understand how PKA works," he says. "This study helps us get a clearer picture of how the PKA protein helps regulate cellular function and disease."


With a background of scattered neutrons, this image shows a model of the II-beta form of PKA. A neutron beam used for imaging (behind gray circle) helped researchers identify a region of II-beta that is likely to give PKA its unique shape.

Credit: William Heller, Oak Ridge National Laboratory

The study, published in the Oct. 10 issue of the Journal of Biological Chemistry as its paper of the week, is a collaboration among researchers at the U of U, University of California, San Diego (UCSD), and Oak Ridge National Laboratory in Tennessee.

The PKA protein comes in four forms, each of which serves as a sensor for a signaling molecule called cyclic AMP (cAMP). When these forms of PKA sense cAMP, they change shape, which researchers believe is critical in determining how PKA works as a biochemical switch.

Many hormones, neurotransmitters and drugs communicate with cells by changing the level of cAMP found within them. Accordingly, PKA helps regulate cellular activity in reaction to different levels of cAMP within cells. Because PKA serves as a master switch in cells, mutations in it lead to a variety of diseases including metabolic disorder, disorders of the brain and nervous system, cancer and cardiovascular ills.

Blumenthal and colleagues focused on a form of PKA called II-beta, a protein found mostly in the brain and fat cells that is suspected of being involved in obesity and diet-induced insulin-resistance associated with type 2 diabetes. II-beta contains two mechanisms for sensing cAMP, each of which unfolds and separates in response to the signaling molecule.

The researchers wanted to know whether both of II-beta's cAMP-sensing mechanisms are required to determine its ability to change shape – a critical factor for its function. To answer this, they removed one of the cAMP sensors and used advanced small-angle neutron scattering imaging, a technology available at Oak Ridge's High Flux Isotope Reactor, and small-angle X-ray scattering at the U of U, each of which produces images that reveal information about the shape and size of molecules. The images showed that II-beta does, indeed, change shape with only one sensor.

"By process of elimination, this must mean that parts of the remaining single sensor of II-beta give it its unique shape and internal architecture," says Susan Taylor, Ph.D., professor of chemistry, biochemistry and pharmacology at UCSD and co-author on the study. "Our findings further narrow and define the key components of II-beta and identify new regions for further study."

Future research should focus on a part of II-beta called the "linker region," which connects the remaining cAMP sensor with a part of II-beta that helps target PKA to specific cell locations, according to Blumenthal. "Based on what we know about II-beta and other forms of PKA, it's likely that the linker region plays a major role in organizing the internal architecture and shape changes the determine the unique biological functions of PKA."

###

The study's co-authors include Jeffrey Copps, Eric V. Smith-Nguyen and Ping Zhang, UCSD Department of Chemistry and Biochemistry and Howard Hughes Medical Institute and William T. Heller, Oak Ridge National Laboratory.

Funding support for this research came, in part, from the U.S. Department of Energy and the National Institutes of Health (grant GM34921).

Phil Sahm | Eurek Alert!
Further information:
http://healthcare.utah.edu/publicaffairs/

More articles from Life Sciences:

nachricht Magic number colloidal clusters
13.12.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Record levels of mercury released by thawing permafrost in Canadian Arctic
13.12.2018 | University of Alberta

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

Magic number colloidal clusters

13.12.2018 | Life Sciences

UNLV study unlocks clues to how planets form

13.12.2018 | Physics and Astronomy

Live from the ocean research vessel Atlantis

13.12.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>