A new thematic minireview series entitled “Prokaryotic protein phosphorylation” appeared in a recent issue of The Journal of Biological Chemistry. Signal transduction mediated by reversible protein phosphorylation has been studied intensely for more than 50 years in eukaryotes. Sadly, understanding the role of prokaryotic protein kinases in phosphatase signaling has come much slower. Elucidation of the pathways in prokaryotes may be of considerable clinical and industrial importance. This minireview series provides an overview of different prokaryotic protein kinases and discusses the wide conservation of protein phosphorylation as a mode of cellular regulation.
In the first minireview, Yossef Av-Gay and colleagues at the University of British Columbia discuss prokaryotic protein Tyr kinases. This review focuses on the bacterial tyrosine kinases, or BY-kinases, and the atypical or “odd” tyrosine kinases that show no homology to eukaryotic or BY-kinases. The BY-kinases are involved in many diverse functions in bacteria, including biofilm formation, virulence, spore formulation, DNA replication and antibiotic resistance. The M. tuberculosis Tyr kinase PtkA gets special attention in this review, as it is a representative example of an “odd” tyrosine kinase. Phosphorylation of a key virulence factor in M. tuberculosis by PtkA highlights the involvement of tyrosine kinases in microbial pathogenesis and represents an unexplored area for drug discovery.
Virginie Molle and Marc Canova at the Universités de Montpellier explore in the second minireview the eukaryoticlike signaling systems in bacterial pathogens. Some of the well-studied bacterial protein kinases are essential virulence factors and modify global host responses during infection. The prokaryotic protein kinases in human pathogens — such as Streptococcus, Mycobacteria, Yersinia and Listeria — are ideal candidates for drug development, because the bacterial kinases are proving to be molecular switches that play key roles in host-pathogen interactions.
In the third minireview, Peter Kennelly at Virginia Polytechnic Institute and State University focuses on phosphorylation of proteins in the domain Archaea. While prokaryotic in morphology, the Archaea share closer evolutionary ties to eukaryotic cells. The protein kinases in the Archaea are structurally related and resemble both eukaryotic Ser/Thr and Tyr kinases. Much less is known about phosphorylation in the Archaea, and much of what we currently know is from S. Solfataricus. Kennelly nicely summaries the protein phosphorylation networks in members of Archaea, and he reveals some of the intriguing questions that remain in the field.
Finally, Nicole LaRonde at the University of Maryland, College Park, reviews microbial RIO, or right-open reading-frame, kinases. The RIO kinases may be the most ancient, as they have been around since before the divergence of Archaea and eubacteria. While it is well established that RIO kinases are essential for the synthesis of new ribosomes in eukaryotes, the role in prokaryotes is unknown. By describing the structures of RIO kinases of Archaea, the search for RIO kinase substrates, the known functions of the RIO kinases and the development of inhibitors using microbial RIO kinases, LaRonde provides support for the probability that archaeal RIO kinases perform similar biological roles to those observed in eukaryotes.
The four minireviews in this series help to broaden our thinking about protein phosphorylation. In an editorial commentary, John Kyriakis, the JBC associate editor overseeing the series, concludes that we need to consider novel, noneukaryotic cell mechanisms when learning about phosphorylation in prokaryotes. While less is known about prokaryotic protein kinases, this is a new and exciting field.
Jenna Hendershot (firstname.lastname@example.org
) earned a B.S. in cellular and molecular biology from Grand Valley State University and is completing her Ph.D. in biological chemistry at the University of Michigan.