Historical background

Serine/threonine/tyrosine phosphorylation of proteins was first described in Eukarya whereas phosphorylation on histidine/aspartate residues was usually associated with bacterial signaling. However, evidence concerning the presence of serine/threonine/tyrosine phosphorylation in bacteria1 has accumulated over the years and today it is clear that this type of protein phosphorylation plays a prominent role in bacterial physiology. Bacteria do possess a number of eukaryotic-like serine/threonine-kinases, but there is also clear evidence for idiosyncratic bacterial serine/threonine- and tyrosine-kinases2 that have evolved independently. Among them, bacterial tyrosine-kinases (BY-kinases) shows no resemblance to eukaryotic-like kinases and they have been identified in a majority of sequenced bacterial genomes3, and are thus considered widespread, if not ubiquitous, in the bacterial kingdom.

About BY-kinases

A typical BY-kinase consists of an N-terminal transmembrane external loop, followed by a cytoplasmic catalytic domain that contains the ATP-binding site and a C-terminal tail of autophosphorylatable tyrosine residues. Depending on their phylogenetic origin, these two domains can be linked in a single polypeptide (see Fig.A) or encoded by two distinct genes (see Fig. B). A distinctive feature of these enzymes is that they use a structural motif known as the P-loop (Walker A and B) to constitute their active site, whereas in Eukarya Walker motifs are found in many ATP/GTPases.

organisation of the Bacterial tyrosine protein kinase (BY-kinase)

The crystal structures reported recently for the cytoplasmic domains of three members of the BY-kinase family brought insights into their autophosphorylation mechanism, their oligomerization and their activation process.The versatility and importance of BY kinases have been well demonstrated in many facets of cellular regulation. They regulate some key enzymes by means of phosphorylation and they participate in polysaccharide synthesis and export, antibiotic resistance, stress response and DNA metabolism4. In addition, recent advances in phosphoproteomics provided snapshots of several bacterial phosphoproteomes and suggest that BY-kinases would be involved in numerous regulatory processes5. BY-kinases represent therefore important regulatory enzymes of bacterial physiology6 and because they have no eukaryotic homologues, they could be considered as potential therapeutic targets7 to combat bacterial infectious diseases.


  1. Ser/Thr/Tyr protein phosphorylation in bacteria - for long time neglected, now well established.
    Deutscher J., Saier M.H. Jr.
    J. Mol. Microbiol. Biotechnol., 2005, 9(3-4):125-131.

  2. Tyrosine-kinases in bacteria: from a matter of controversy to the status of key regulator enzymes.
    Béchet E., Guiral S., Torres S., Mijakovic I., Cozzone A.J., Grangeasse C.
    Amino Acids, 2009, 37(3):499-507.

  3. Protein-tyrosine phosphorylation in Bacillus subtilis.
    Mijakovic I., Petranovic D., Bottini N., Deutscher J., Jensen P.R.
    J. Mol. Microbiol. Biotechnol., 2005, 9:189-197.

  4. Bacterial Protein-Tyrosine kinases.
    Shi L., Kobir A., Jers C., Mijakovic I.
    Current Proteomics., 2010, 7(3):188-194.

  5. Phosphoproteomics in bacteria: towards a systemic understanding of bacterial phosphorylation networks.
    Jers C., Soufi B., Grangeasse C., Deutscher J., Mijakovic I.
    Expert Rev. Proteomics., 2008, 5(4):619-627.

  6. Tyrosine phosphorylation: an emerging regulatory device of bacterial physiology.
    Grangeasse C., Cozzone A.J., Deutscher J., Mijakovic I.
    Trends Biochem. Sci., 2007, 32:86-94.

  7. Bacterial tyrosine-kinases: Structure-function analysis and therapeutic potential.
    Grangeasse C., Terreux R., Nessler S.
    Bioch. Bioph. Acta., 2010, 1804:628-634.

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