title: Cross-phosphorylation of bacterial serine/threonine and tyrosine protein kinases on key regulatory residues.
abstract: Bacteria possess protein serine/threonine and tyrosine kinases which resemble eukaryal kinases in their capacity to phosphorylate multiple substrates. We hypothesized that the analogy might extend further, and bacterial kinases may also undergo mutual phosphorylation and activation, which is currently considered as a hallmark of eukaryal kinase networks. In order to test this hypothesis, we explored the capacity of all members of four different classes of serine/threonine and tyrosine kinases present in the firmicute model organism Bacillus subtilis to phosphorylate each other in vitro and interact with each other in vivo. The interactomics data suggested a high degree of connectivity among all types of kinases, while phosphorylation assays revealed equally wide-spread cross-phosphorylation events. Our findings suggest that the Hanks-type kinases PrkC, PrkD, and YabT exhibit the highest capacity to phosphorylate other B. subtilis kinases, while the BY-kinase PtkA and the two-component-like kinases RsbW and SpoIIAB show the highest propensity to be phosphorylated by other kinases. Analysis of phosphorylated residues on several selected recipient kinases suggests that most cross-phosphorylation events concern key regulatory residues. Therefore, cross-phosphorylation events are very likely to influence the capacity of recipient kinases to phosphorylate substrates downstream in the signal transduction cascade. We therefore conclude that bacterial serine/threonine and tyrosine kinases probably engage in a network-type behavior previously described only in eukaryal cells.
authors.affiliation: SysBio, Department of Chemical and Biological Engineering, Chalmers University of Technology Göteborg, Sweden.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: UMR1319 Micalis, Institut National de Recherche Agronomique Jouy-en-Josas, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pigeonneau
authors.affiliation: Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen Tübingen, Germany.
authors.forename: Vaishnavi
authors.initials: V
authors.lastname: Ravikumar
authors.affiliation: Division of Biology, Faculty of Science, Zagreb University Zagreb, Croatia.
authors.forename: Paula
authors.initials: P
authors.lastname: Dobrinic
authors.affiliation: Proteome Center Tübingen, Interfaculty Institute for Cell Biology, University of Tübingen Tübingen, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Macek
authors.affiliation: Division of Biology, Faculty of Science, Zagreb University Zagreb, Croatia.
authors.forename: Damjan
authors.initials: D
authors.lastname: Franjevic
authors.affiliation: UMR1319 Micalis, Institut National de Recherche Agronomique Jouy-en-Josas, France.
authors.forename: Marie-Francoise
authors.initials: MF
authors.lastname: Noirot-Gros
authors.affiliation: SysBio, Department of Chemical and Biological Engineering, Chalmers University of Technology Göteborg, Sweden.
authors.forename: Ivan
authors.initials: I
authors.lastname: Mijakovic
keywords: bacterial protein kinase; kinase activation; phosphorylation cascade; protein kinase cross-talk; protein phosphorylation