Bacterial Protein-Tyrosine Kinases

Lei      Shi; Ahasanul      Kobir; Carsten      Jers; Ivan      Mijakovic

Abstract

Bacteria and Eukarya share essentially the same family of protein-serine/threonine kinases, also known as the Hanks-type kinases. However, when it comes to protein-tyrosine phosphorylation, bacteria seem to have gone their own way. Bacterial protein-tyrosine kinases (BY-kinases) are bacterial enzymes that are unique in exploiting the ATP/GTPbinding Walker motif to catalyze phosphorylation of protein tyrosine residues. Characterized for the first time only a decade ago, BY-kinases have now come to the fore. Important regulatory roles have been linked with these enzymes, via their involvement in exopolysaccharide production, virulence, DNA metabolism, stress response and other key functions of the bacterial cell. BY-kinases act through autophosphorylation (mainly in exopolysaccharide production) and phosphorylation of other proteins, which have in most cases been shown to be activated by tyrosine phosphorylation. Protein-tyrosine phosphorylation in bacteria is particular with respect to very low occupancy of phosphorylation sites in vivo; this has represented a major challenge for detection techniques. Only the recent breakthroughs in gel-free high resolution mass spectrometry allowed the systematic detection of phosphorylated tyrosines by phosphoprotomics studies in bacteria. Other pioneering studies conducted in recent years, such as the first structures of BY-kinases and biochemical and phyiological studies of new BY-kinase substrates significantly furthered our understanding of these enzymes and highlighted their importance in bacterial physiology. Having no orthologues in Eukarya, BY-kinases are receiving a growing attention from the biomedical field, since they represent a particularly promising target for anti-bacterial drug design.

Keywords: Protein-tyrosine kinase, BY-kinase, bacteria, protein phosphorylation, phosphoproteome, signal transduction, cellular regulation, Protein-serine/ threonine kinases, Hanks-type kinases, Protein-tyrosine phosphorylation, Virulence, DNA metabolism, Stress response, Gel0free high resolution mass spectrometry, Biomedical field, Anti-bacterial drug design, Post- Translational modifications, Protein glycosylation, Co-localization, Anti-sigma factor RseA, Colanic acid synthesis, Heat-shock genes, Protease complex responsible, Immune-affinity, Gold-chloride electrochemistry, Inhibitory drugs