title: Substrate Specificity of theBacillus subtilisBY-Kinase PtkA Is Controlled by Alternative Activators: TkmA and SalA.
abstract: Bacterial protein-tyrosine kinases (BY-kinases) are known to regulate different aspects of bacterial physiology, by phosphorylating cellular protein substrates. Physiological cues that trigger BY-kinases activity are largely unexplored. InProteobacteria, BY-kinases contain a cytosol-exposed catalytic domain and a transmembrane activator domain in a single polypeptide chain. InFirmicutes, the BY-kinase catalytic domain and the transmembrane activator domain exist as separate polypeptides. We have previously speculated that this architecture might enable theFirmicutesBY-kinases to interact with alternative activators, and thus account for the observed ability of these kinases to phosphorylate several distinct classes of protein substrates. Here, we present experimental evidence that supports this hypothesis. We focus on the modelFirmicute-type BY-kinase PtkA fromBacillus subtilis, known to phosphorylate several different protein substrates. We demonstrate that the transcriptional regulator SalA, hitherto known as a substrate of PtkA, can also act as a PtkA activator. In doing so, SalA competes with the canonical PtkA activator, TkmA. Our results suggest that the respective interactions of SalA and TkmA with PtkA favor phosphorylation of different protein substratesin vivoandin vitro. This observation may contribute to explaining how specificity is established in the seemingly promiscuous interactions of BY-kinases with their cellular substrates.
authors.affiliation: Division of Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology Gothenburg, Sweden.
authors.forename: Abderahmane
authors.initials: A
authors.lastname: Derouiche
authors.affiliation: Division of Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology Gothenburg, Sweden.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Division of Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology Gothenburg, Sweden.
authors.forename: Aida
authors.initials: A
authors.lastname: Kalantari
authors.affiliation: Division of Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of TechnologyGothenburg, Sweden; Novo Nordisk Foundation Center for Biosustainability, Technical University of DenmarkLyngby, Denmark.
authors.forename: Ivan
authors.initials: I
authors.lastname: Mijakovic
keywords: bacterial protein-tyrosine kinase; kinase activator; kinase specificity; protein phosphorylation; transcription factor