Protein-tyrosine phosphorylation interaction network in Bacillus subtilis reveals new substrates, kinase activators and kinase cross-talk.
Signal transduction in eukaryotes is generally transmitted through phosphorylation cascades that involve a complex interplay of transmembrane receptors, protein kinases, phosphatases and their targets. Our previous work indicated that bacterial protein-tyrosine kinases and phosphatases may exhibit similar properties, since they act on many different substrates. To capture the complexity of this phosphorylation-based network, we performed a comprehensive interactome study focused on the protein-tyrosine kinases and phosphatases in the model bacterium Bacillus subtilis. The resulting network identified many potential new substrates of kinases and phosphatases, some of which were experimentally validated. Our study highlighted the role of tyrosine and serine/threonine kinases and phosphatases in DNA metabolism, transcriptional control and cell division. This interaction network reveals significant crosstalk among different classes of kinases. We found that tyrosine kinases can bind to several modulators, transmembrane or cytosolic, consistent with a branching of signaling pathways. Most particularly, we found that the division site regulator MinD can form a complex with the tyrosine kinase PtkA and modulate its activity in vitro. In vivo, it acts as a scaffold protein which anchors the kinase at the cell pole. This network highlighted a role of tyrosine phosphorylation in the spatial regulation of the Z-ring during cytokinesis.
Institut National de la Recherche Agronomique, UMR1319 Micalis Jouy-en-Josas, France ; Systems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology Gothenburg, Sweden.
Lei
L
Shi
Institut National de la Recherche Agronomique, UMR1319 Micalis Jouy-en-Josas, France.
Nathalie
N
Pigeonneau
Institut National de la Recherche Agronomique, UMR1319 Micalis Jouy-en-Josas, France.
Magali
M
Ventroux
Institut National de la Recherche Agronomique, UMR1319 Micalis Jouy-en-Josas, France ; Systems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology Gothenburg, Sweden.
Abderahmane
A
Derouiche
Systems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology Gothenburg, Sweden.
Vladimir
V
Bidnenko
Institut National de la Recherche Agronomique, UMR1319 Micalis Jouy-en-Josas, France ; Systems and Synthetic Biology, Department of Chemical and Biological Engineering, Chalmers University of Technology Gothenburg, Sweden.
Ivan
I
Mijakovic
Institut National de la Recherche Agronomique, UMR1319 Micalis Jouy-en-Josas, France.
Marie-Françoise
MF
Noirot-Gros
bacterial cell division; bacterial protein kinase; bacterial signaling; protein phosphorylation; protein-protein network