New technique switches key biomolecules on and off

December 13, 2016

A new technique that will allow scientists to determine the effects of turning on and off a set of molecules involved in almost every cellular pathway, determine their downstream effects, and uncover new drug targets has been developed by researchers at the University of Illinois at Chicago.

The finding is reported in the Proceedings of the National Academy of Sciences.

Protein kinases are enzymes involved in almost every biological process. These molecules perform a single action - they transfer phosphate from the energy molecule ATP to other enzymes and proteins. The process is a key mechanism of regulatory control and allows cells to perform all of their functions.

Several hundred different kinases work to phosphorylate various proteins and drive the entire range of cellular activities. Understanding precisely how kinases work would reveal cellular pathways that drive cells to become cancerous and identify novel drug targets.

Until now, it was difficult to study cellular processes triggered by specific kinases that turn on only briefly, says Andrei Karginov, assistant professor of pharmacology in the UIC College of Medicine.

"Previously, we had the ability to artificially turn on a kinase, but we didn't know how to turn it off," Karginov said. "So what we could see was only the result of that kinase being on for a long time."

That approach has proved useful to study the prolonged cancer-causing effects of some kinases, Karginov said.

"But, in living cells, kinases are often turned only for a set period of time, and the duration of this activation often dictates what will happen to the cell," he said.

"To mimic this transient action we had come up with a new strategy."

The new procedure allows scientists to turn kinases on, and then off - providing a powerful tool for studying the effects of kinases as they actually work in the body.

The researchers used two protein-engineering techniques to switch on and switch off one kinase, called tyrosine kinase c-Src. They were able to observe a series of structural changes when they turned the enzyme on for various periods of time.

The first wave of changes, where the cell seemed to expand and then contract, was driven by kinase activation and inactivation. Interestingly, a second expansion sometimes occurred after the kinase had been switched off - depending on how long it had been left on.

The experiment demonstrated that even short-term activation of a kinase can have a long-lasting effect on cell behavior, and allowed researchers to identify the molecular mechanism driving these events.
-end-
Asrar Malik, Jennifer Klomp, Vincent Huyot, Anne-Marie Ray, and Kerrie Collins of the UIC department of pharmacology are co-authors on the paper.

This research was funded by the National Institutes of Health grants R21CA159179 and T32 HL007829-22, the Chicago Biomedical Consortium and the UIC Center for Clinical and Translational Science grant UL1TR000050.

University of Illinois at Chicago

Related Cellular Pathway Articles from Brightsurf:

Cellular survivors
When it comes to complex life -- that of the multicellular variety -- cell death can be just as important as survival.

The Wnt pathway gets even more complicated
A new role for Casein Kinase-1 on RNF43 is identified - Study by Tadasuke Tsukiyama and IMBA - Institute of Molecular Biotechnology of the Austrian Academy of Sciences group leader Bon-Kyoung Koo published in Nature Communications

Discovered: Cellular pathway involved in resistance to Ebola virus and SARS-like coronaviruses
Researchers working in human cells have identified a new pathway that targets a common vulnerability in several different pandemic viruses.

Researchers discover critical new allergy pathway
Researchers at Johns Hopkins Bloomberg School of Public Health have identified the sequence of molecular events by which tiny, tick-like creatures called house dust mites trigger asthma and allergic rhinitis.

New drug pathway linked with tuberous sclerosis
Researchers in the Translational Neuroscience Center have discovered that the heat shock protein cascade may represent druggable targets for tuberous sclerosis

New pathway to attack tumor cells identified
A study led by the Institut de Neurociències (INc-UAB) describes a new strategy to tackle cancer, based on inducing a potent stress in tumor causing cell destruction by autophagy.

New membranes for cellular recycling
Cells produce the shell of the autophagosomes on the spot.

A new pathway to 'reprogram' killer cells
Killer cells of the immune system detect and kill infected cells or cancer cells.

Uncovering the pathway to wine's acidity
University of Adelaide wine researchers say their latest discovery may one day lead to winemakers being able to manipulate the acidity of wines without the costly addition of tartaric acid.

A new, unified pathway for prebiotic RNA synthesis
Adding to support for the RNA world hypothesis, Sidney Becker and colleagues have presented what's not been shown before -- a single chemical pathway that could generate both the purine and pyrimidine nucleosides, the key building blocks of RNA.

Read More: Cellular Pathway News and Cellular Pathway Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.