Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers Look Inside to Reveal Workings of a Powerful Biochemical Switch


PKA helps regulate basic cellular functions, leads to disease when mutated

Using X-rays and neutron beams, a team of researchers from the University of Utah, University of California, San Diego School of Medicine and Oak Ridge National Laboratory have 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.

A molecular model of the protein, PKA II-beta, based on neutron scattering with solvent contrast is laid over the neutron scattering data from the Bio-SANS instrument at DOE’s HFIR research facility. The neutron beam is in the left behind the grey circle and the scattered neutrons create the pattern in the rest of the background. A research team from ORNL, UCSD, and the University of Utah is using neutron and X-ray data to understand the role of this protein in regulating basic cellular functions. Image credit: William Heller/ORNL

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.”

The study, published in the Oct. 10 issue of the Journal of Biological Chemistry as its paper of the week, features research conducted using the Bio-SANS instrument at the Oak Ridge National Laboratory (ORNL) High Flux Isotope Reactor (HFIR), a DOE Office of Science User Facility.

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 disorders, disorders of the brain and nervous system, cancer and cardiovascular ills.

Blumenthal and colleagues focused on a form of PKA called II-beta (two-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 structures for sensing cAMP, each of which cause II-beta to change its shape in response to the signaling molecule.

The researchers wanted to know whether both of II-beta’s cAMP-sensing structures 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 small-angle neutron scattering at HFIR, and small-angle X-ray scattering at U of U, each of which reveals information about the shape and size of molecules. The results of the study 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 the University of California, San Diego, 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 determine the unique biological functions of each form 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 from the National Institutes of Health (grant GM34921). The Center for Structural Molecular Biology operates Bio-SANS, the HFIR instrument used for the neutron scattering experiments, and is supported by the DOE Office of Science, which also supports HFIR.

UT-Battelle manages ORNL for the Department of Energy's Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit

Contact Information

Katie Bethea
Oak Ridge National Laboratory

Katie Bethea | newswise

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>