Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New strategy developed to study disease: Reveals insights into cancer and treatment leads

09.03.2006


For the first time, Johns Hopkins researchers were able to easily jumpstart the activity of a well-known cancer protein in live cells with a small molecule, a strategy that pinpointed key players in the cancer process and can be used to determine new therapeutic targets. What’s more, the scientists’ study, published in the March 3 issue of Science, identifies a simple method to further understand the complex mechanisms that underlie cancer as well as other diseases and may provide an easy model to screen for new cancer drugs.



"Our study reveals a new way to study proteins in live cells, in this case, a tyrosine kinase implicated in causing cancer," says the study’s lead author, Philip A. Cole, M.D., Ph.D., director of the Department of Pharmacology and Molecular Sciences at The Johns Hopkins University School of Medicine. "This approach helped identify potentially important therapeutic targets and in the future may provide a method to easily screen cancer treatments."

In the study, Cole and his colleagues examined the tyrosine kinase Src (pronounced SARK), a clinically important cancer protein that scientists have heavily studied but do not completely understand. The Johns Hopkins researchers developed a special mutated version of the Src protein and incorporated it into live animal cells. The mutated version was inactive but contained an "ignition switch" that would turn it back on. They determined that the small molecule, imidazole, could act as the key. Imidazole fit into a pocket in the mutated structure of the Src protein, which mended the structure and reinstated Src’s activity. Removal of imidazole quickly shut the protein off again.


"This strategy provided a controlled environment to study Src," says Cole. "This helped us uncover some new and unexpected insights into how the cancer protein creates its havoc, as well as new treatment leads." For one, the model provided evidence that Src interacts with CrkL, a signaling protein not previously known to be targeted by Src’s actions. The study also found direct evidence that Src activates MAP kinase pathways, which help transfer information from growth factors, molecules that aid in the development of cancer cells. Previously the role of Src in these pathways was controversial.

"Understanding the functions of different proteins in normal states and disease states is crucial for treatment development because it can help identify new therapeutic targets," says Cole. Insights into tyrosine kinases could be particularly important for determining new cancer treatments, since scientists think that many different types are involved. "For example, Gleevec, which is used to treat gastrointestinal stromal tumors and chronic myeloid leukemia, is the most successful magic bullet against cancer in many years and works by blocking tyrosine kinase activity," Cole says.

As a next step, Cole and his colleagues plan to further examine the role of Src in cancer using their new model. They also plan to adapt the approach to develop a drug screen.

In the future, it also may be possible to use their chemical technique to mend mutated proteins found in people with certain genetic diseases, according to Cole. For example, the immune system disorder agammaglobulinemia involves mutated tyrosine kinases. Possibly researchers could identify a small molecule that rescues the activity of the mutated tyrosine kinases in the same way that imidazole corrected the structure of the mutated Src and jumpstarted its activity.

Eric Vohr | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus 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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>