Abstract
Bacillus subtilis two-component system DegS/U is well known for the complexity of its regulation. The cytosolic sensory kinase DegS does not receive a single predominant input signal like most two-component kinases, instead it integrates a wide array of metabolic inputs that modulate its activity. The phosphorylation state of the response regulator DegU also does not confer a straightforward “on/off” response; it is fine-tuned and at different levels triggers different sub-regulons. Here we describe serine phosphorylation of the DegS sensing domain, which stimulates its kinase activity. We demonstrate that DegS phosphorylation can be carried out by at least two B. subtilis Hanks-type kinases in vitro, and this stimulates the phosphate transfer towards DegU. The consequences of this process were studied in vivo, using phosphomimetic (Ser76Asp) and non-phosphorylatable (Ser76Ala) mutants of DegS. In a number of physiological assays focused on different processes regulated by DegU, DegS S76D phosphomimetic mutant behaved like a strain with intermediate levels of DegU phosphorylation, whereas DegS S76A behaved like a strain with lower levels of DegU phophorylation. These findings suggest a link between DegS phosphorylation at serine 76 and the level of DegU phosphorylation, establishing this post-translational modification as an additional trigger for this two-component system.
Highlights
Two-component systems are a ubiquitous means of signal transduction in bacteria [1]
Concluding remarks Here we describe, to the best of our knowledge, the first example of a bacterial two component sensory kinase that is regulated via serine phosphorylation of its input domain by a Hanks type Ser/Thr kinase
The ensuing phenotypes may be caused by conformational changes caused by the mutations, which are entirely unrelated to phosphorylation
Summary
Two-component systems are a ubiquitous means of signal transduction in bacteria [1]. The first, signal-receiving component is a sensory histidine kinase that is triggered by a stimulus binding or otherwise affecting its sensing domain. The histidine kinases of the two-component systems are known to be highly specific, i.e. exhibiting low level of cross-talk with non-cognate response regulators [2] Another major group of bacterial kinases involved in signal transduction is the Hanks type serine/threonine kinases [3,4]. A recent phosphoproteomic study in Bacillus subtilis, identified the two-component system histidine kinase DegS as being phosphorylated on the residue serine, located in the signal sensing domain [8]. This implied the existence of a new type of crosstalk between two phosphorylation systems, namely one in which a presently unknown serine kinase would phosphorylate the two-component sensory histidine kinase
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