Is Bacillus subtilis PtkA regulated like a cyclin-dependent kinase?

Bacillus subtilis PtkA was the first bacterial protein-tyrosine kinase shown to phosphorylate cellular proteins and regulate their activity. My group has mapped an extensive regulatory network around this kinase.

PtkA is known to be activated by three activator proteins and when active, it phosphorylates over a dozen cellular protein substrates, regulating their activity or localization. PtkA is also inhibited via an interaction with the protein DefA. The known regulatory network of PtkA is quite detailed, but entirely static.

It describes the interactions, but does not clarify how the regulation actually works. Which substrates get phosphorylated at what times, and what are the molecular cues that trigger this?

This question has no clear answer not only in B. subtilis, but also in other bacteria where BY-kinases have been studied. Have we have been looking in the wrong place – searching for extracellular molecular cues? Such signals have never been found. In this project I propose to test a different hypothesis to explain BY-kinase control.

Namely, whether PtkA might be controlled similarly to cyclin dependent kinases, by being recruited to different tasks by its activators/inhibitors, whose concentration, localization and availability for interaction varies during the cell cycle.

If this hypothesis survives the test, it would have a profound impact on the field, especially in pathogenic bacteria, where BY-kinases represent viable drug targets (absent in human cells).