From global phosphoproteomics to individual proteins: the case of translation elongation factor eEF1A

Abstract

Phosphoproteomics is often aimed at deciphering the modified components of signaling pathways in certain organisms, tissues and pathologies. Phosphorylation of housekeeping proteins, albeit important, usually attracts less attention. Here, we provide targeted analysis of eukaryotic translation elongation factor 1A (eEF1A), which is the main element of peptide elongation machinery. There are 97% homologous A1 and A2 isoforms of eEF1A; their expression in mammalian tissues is mutually exclusive and differentially regulated in development. The A2 isoform reveals proto-oncogenic properties and specifically interacts with some cellular proteins. Several tyrosine residues shown experimentally to be phosphorylated in eEF1A1 are hardly solution accessible, so their phosphorylation could be linked with structural rearrangement of the protein molecule. The possible role of tyrosine phosphorylation in providing the background for structural differences between the ‘extended’ A1 isoform and the compact oncogenic A2 isoform is discussed. The ‘road map’ for targeted analysis of any protein of interest using phosphoproteomics data is presented.

Keywords::

• phosphoproteome
• protein isoforms
• protein spatial structure
• translation elongation factor 1A
• tyrosine phosphorylation

Acknowledgements

The authors wish to thank V Filonenko for useful comments and M Dadlez for inspiring discussions.

Financial & competing interests disclosure

The study was supported by the State Key Laboratory of Molecular and Cell Biology funds. The authors appreciate the contribution of the collaborative grants of the National Academy of Sciences of Ukraine with the Russian Academy of Sciences and Centre National de la Recherche Scientifique of France, as well as the collaboration agreement between the National Academy of Sciences of Ukraine and the Polish Academy of Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.