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


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:

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>