Phosphorylation-mediated signalling – a new era?

Phosphorylation-mediated signalling – a new era?

Phosphorylation-mediated signalling – a new era?

Prof. Claire Eyers

Department of Biochemistry & Systems Biology, University of Liverpool

Protein phosphorylation is a ubiquitous post-translational modification (PTM) that regulates all aspects of life. To date, investigation of human phosphorylation-mediated cell signalling has focused on canonical phosphorylation of serine (Ser), threonine (Thr) and tyrosine (Tyr) residues. However, mounting evidence indicates that phosphorylation of histidine also plays a central role in regulating human cell biology. Biochemical and phosphoproteomics workflows rely on acidic conditions or elevated temperatures for analysis, which are incompatible with the analysis of acid-labile phosphorylation such as histidine. Consequently, the extent of ‘non-canonical’ phosphorylation in humans and other vertebrates is unknown. We have developed an Unbiased Phosphopeptide enrichment strategy based on Strong Anion Exchange (SAX) chromatography (UPAX), which permits enrichment of acid-labile phosphopeptides for characterisation by mass spectrometry. This approach has allowed us to identify extensive and positional phosphorylation patterns on histidine, arginine, lysine, aspartate, glutamate and cysteine in human cell extracts. Our data reveals the previously unappreciated diversity of protein phosphorylation in human cells, and opens up avenues for exploring roles of acid-labile phosphorylation, and their interplay with other PTMs, on human proteins.

Claire E. Eyers is Professor of Biological Mass Spectrometry in the Institute of Systems, Molecular & Integrative Biology at the University of Liverpool (UoL), Director of the Centre for Proteome Research (CPR), and Associate Pro Vice Chancellor (Research & Impact) for the Faculty of Health and Life Sciences. Having obtained a PhD (2002) in Biochemistry from the University of Dundee (Prof. Sir P. Cohen), she undertook postdoctoral studies at the University of Colorado, Boulder (Prof. N. Ahn) and then in the Michael Barber Centre for Mass Spectrometry, University of Manchester (Prof. S. Gaskell), where she became Acting Director (2009–2013).  Her research exploits biophysical and biochemical methodologies to understand the structure and relevance of post-translational modifications (PTMs) and their roles in regulating cellular signalling in health and disease. She has established expertise in the development of mass spectrometric (MS)-based methods, and exploits separation technologies, including ion mobility spectrometry (IMS), for the structural investigation of proteins and the effects of PTMs and ligand binding.

Prof. Eyers has held an independent American Heart Association (AHA) fellowship, for which she was awarded an AHA postdoctoral prize, and a Royal Society Dorothy Hodgkin Fellowship (2007-11). She is currently Chair of BBSRC committee D, Deputy Chair of the BBSRC sLOLA committee and formerly trustee and executive committee member of the British Mass Spectrometry Society. She is an active STEM ambassador.

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