Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Global signaling study suggests cancer link to protein promiscuity

17.11.2005


Haphazard activation of secondary signaling pathways may fuel cancer’s genesis



When found at abnormally high concentrations, two proteins implicated in many human cancers have the potential to spur indiscriminate biochemical signaling inside cells, chemists at Harvard University have found. Their finding may expand scientists’ current understanding of oncogenesis -- that cancer arises when an oncoprotein becomes overactive, ramping up the biochemical pathways that it normally activates -- suggesting that an important additional mechanism could be the inappropriate activation of numerous secondary pathways.

"Our data offer a new way to think about cancer, adding to the current paradigm," says Gavin MacBeath, an assistant professor of chemistry and chemical biology in Harvard’s Faculty of Arts and Sciences and co-author of a paper published in the journal Nature. "We present the hypothesis that an important component of oncogenesis is the ability of proteins to turn on alternative, secondary signaling pathways when overexpressed, rather than simply upregulating primary pathways."


MacBeath and colleagues studied the four human ErbB receptors, which set in motion widely studied cellular processes including cell migration, adhesion, growth and death. These receptors span the cell membrane; the external portion binds free growth factors, creating biochemical signals propagated inside the cell.

Each ErbB receptor has multiple intracellular binding sites where proteins can dock, but MacBeath’s group found that only two of the four ErbB proteins, known as EGFR and ErbB2, become dramatically more "promiscuous" -- able to recruit and activate a large number of different signaling proteins -- when present at high concentrations.

"These two promiscuous ErbB proteins are known to be overactive in many human cancers, suggesting that their ability to turn on rampant signaling may contribute to their high oncogenic potential," MacBeath says. "This newfound link may also offer alternative strategies for therapeutic intervention. Many of today’s cancer pharmaceuticals work by targeting individual receptors such as EGFR and ErbB2. Our work suggests that new drugs could target critical secondary pathways that are inappropriately activated by promiscuous proteins."

The researchers studied interactions between signaling proteins and the ErbB receptors using a protein microarray technique developed by MacBeath in 2000, when he was a research fellow in Harvard’s Bauer Center for Genomic Research. This method can rapidly and simultaneously assess the strength of interactions among tens of thousands of proteins genome-wide. The current research analyzed the interactions between 159 proteins and 33 binding sites on the four ErbB receptors. The scientists looked not only at whether a given protein-receptor pair interacted, but also how strongly.

Steve Bradt | EurekAlert!
Further information:
http://www.harvard.edu

More articles from Studies and Analyses:

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Oxygen loss in the coastal Baltic Sea is “unprecedentedly severe”
05.07.2018 | European Geosciences Union

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>