Researchers at the University of Liverpool have made a major breakthrough in the field of cell signalling.
In humans, signalling in cells normally regulates cell growth and repair. However, abnormal cell signalling contributes to many diseases, including cancer and neurodegeneration. Therefore, identifying specific proteins that control cell signalling in healthy and disease states could help accelerate the discovery of disease biomarkers and drug targets.
Using a new analytical workflow involving mass spectrometry, a team from the university's Department of Biochemistry led by Professor Claire Eyers has shown that the phenomenon of protein modification (phosphorylation) in cell signalling is far more diverse and complex than previously thought. This study, published in The EMBO Journal, opens up a whole new area for bioscience and clinical researchers to explore.
Protein phosphorylation, which involves the addition of phosphate groups to proteins, is a key regulator of protein function, and defining site-specific phosphorylation is essential to understand basic and disease biology.
In vertebrates, research has primarily focused on phosphorylation of the amino acids serine, threonine and tyrosine. However, mounting evidence suggests that phosphorylation of other 'non-canonical' amino acids also regulates critical aspects of cell biology.
Unfortunately, standard methods of characterisation of protein phosphorylation are largely unsuitable for the analysis of these novel types of non-canonical phosphorylation. Consequently, the complete landscape of human protein phosphorylation has, until now, remained unexplored.
This study reports on a new phosphopeptide enrichment strategy, which permits identification of histidine, arginine, lysine, aspartate, glutamate and cysteine phosphorylation sites on human proteins by mass spectrometry-based phosphoproteomics.
Remarkably, the researchers found that the number of unique 'non-canonical' phosphorylation sites is approximately one-third of the number of sites of phosphorylation observed on the more well-studied serine, threonine and tyrosine residues.
Lead researcher Professor Claire Eyers, Director of the Centre for Proteome Research in the Institute of Integrative Biology, said: "The novel non-canonical phosphorylation sites reported in this resource are likely to represent only the tip of the iceberg; identifying the diverse phosphorylation landscape likely to exist across vertebrate and non-vertebrate organisms is an important challenge for the future.
"The diversity and prevalence of multiple non-canonical phosphorylation sites raises the question of how they contribute to global cell biology, and whether they might represent biomarkers, drug targets or anti-targets in disease-associated signalling networks.
"The mass-spectrometry-based analytical workflow that we have developed will allow scientists from around the world to define and understand regulated changes in these novel types of protein modifications in a high throughput manner, which we have demonstrated are widespread in human cells."
The research is featured on the front cover of the latest edition of The EMBO Journal.
The study was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and North West Cancer Research.
Nicola Frost | EurekAlert!
How cells stick together tightly
05.11.2019 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Achilles Heel of Tumour Cells
05.11.2019 | Julius-Maximilians-Universität Würzburg
An international research group has observed new quantum properties on an artificial giant atom and has now published its results in the high-ranking journal Nature Physics. The quantum system under investigation apparently has a memory - a new finding that could be used to build a quantum computer.
The research group, consisting of German, Swedish and Indian scientists, has investigated an artificial quantum system and found new properties.
Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory have reported a new mechanism to speed up the charging of lithium-ion...
Northwestern University chemists have used visible light and extremely tiny nanoparticles to quickly and simply make molecules that are of the same class as...
Almost everyone uses nanometer-sized alumina these days - this mineral, among others, constitutes the skeleton of modern catalytic converters in cars. Until now, the practical production of nanocorundum with a sufficiently high porosity has not been possible. The situation has changed radically with the presentation of a new method of nanocorundum production, developed as part of a German-Polish cooperation of scientists from Mülheim an der Ruhr and Cracow.
High temperatures and pressures, processes lasting for even dozens of days. Current methods of producing nanometer-sized alumina, a material of significant...
Quantum mechanics is embracing patterns of light to create an alphabet that can be leveraged to build a light-based quantum network
Structured light is a fancy way to describe patterns or pictures of light, but deservedly so as it promises future communications that will be both faster and...
05.11.2019 | Event News
30.10.2019 | Event News
02.10.2019 | Event News
05.11.2019 | Information Technology
05.11.2019 | Life Sciences
05.11.2019 | Earth Sciences