New Research on Cell signaling
The University of Liverpool researchers has made a major breakthrough in the field of cell signaling.
In humans, signaling in cells normally regulates cell growth and repair. However, abnormal cell signaling contributes to many diseases, including cancer and neurodegeneration. Therefore, identifying specific proteins that control cell signaling in health and disease states could help accelerate the discovery of certain disease biomarkers & drug targets.
By using a new analytical workflow involving mass spectrometry, a research team from the Department of Biochemistry- the University of Liverpool- led by Professor Claire Eyers has shown now that the phenomenon of protein modification (phosphorylation) in cell signaling is far more diverse and complex than previously thought. This research study, published in The EMBO Journal, opens up a whole new area for bioscience & clinical researchers to explore.
Protein phosphorylation is a process that involves the addition of phosphate groups to proteins. It is a key regulator of protein function, and defining site-specific phosphorylation is essential to understand basic and disease biology. In vertebrates, the study has primarily focused on phosphorylation of the amino acids serine, threonine, & tyrosine. However, mounting evidence of the study suggests that phosphorylation of other “non-canonical” amino acids also regulates critical aspects of cell biology.
Unfortunately, standard methods of characterization of protein phosphorylation are largely unsuitable for the analysis of these novel non-canonical phosphorylation types. Consequently, the complete landscape of the human protein phosphorylation has remained unexplored.
The research reports on a new phosphopeptide enrichment strategy, which permits the identification of histidine, lysine, arginine, aspartate, glutamate, & cysteine phosphorylation sites on human proteins by mass spectrometry technique-based phosphoproteomics.
Remarkably, the scientists found that the number of unique “non-canonical” phosphorylation sites is approximately one-third of the number of phosphorylation sites observed on the more well-studied serine, threonine & tyrosine residues.
Lead researcher of the team, Professor Claire Eyers who is the Director of the Centre for Proteome Research (Institute of Integrative Biology) said that the novel non‐canonical phosphorylation sites reported are likely to represent only the tip of the iceberg; identifying the diverse phosphorylation landscape likely to exist across vertebrate & non‐vertebrate organisms is an important challenge for the future.
The diversity & prevalence of multiple non‐canonical phosphorylation sites raises the question of how these contribute to global cell biology, and whether they can represent the biomarkers, drug targets or anti‐targets in disease‐associated signaling 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.