Opposing pairs of serine protein kinases and phosphatases transmit signals of environmental stress to activate a bacterial transcription factor.
The general stress response of the bacterium Bacillus subtilis is governed by a signal transduction network that regulates activity of the sigma(B) transcription factor. We show that this network comprises two partner-switching modules, RsbX-RsbS-RsbT and RsbU-RsbV-RsbW, which contribute to regulating sigma(B). Each module consists of a phosphatase (X or U), an antagonist protein (S or V), and a switch protein/kinase (T or W). In the downstream module, the W anti-sigma factor is the primary regulator of sigma(B) activity. If the V antagonist is phosphorylated, the W switch protein binds and inhibits sigma(B). If V is unphosphorylated, it complexes W, freeing sigma(B) to interact with RNA polymerase and promote transcription. The phosphorylation state of V is controlled by opposing kinase (W) and phosphatase (U) activities. The U phosphatase is regulated by the upstream module. The T switch protein directly binds U, stimulating phosphatase activity. The T-U interaction is governed by the phosphorylation state of the S antagonist, controlled by opposing kinase (T) and phosphatase (X) activities. This partner-switching mechanism provides a general regulatory strategy in which linked modules sense and integrate multiple signals by protein-protein interaction.
Yang
X
X
Department of Food Science and Technology, University of California, Davis 95616, USA.
Kang
C M
CM
Brody
M S
MS
Price
C W
CW
D001412:Bacillus subtilis / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D029968:Escherichia coli Proteins; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C086522:RsbV protein, Bacteria; C080358:RsbW protein, bacteria; C079011:SigB protein, Bacteria; D012808:Sigma Factor; D014157:Transcription Factors; C098923:rssB protein, E coli; D010744:Phosphoric Monoester Hydrolases; C091162:RsbU protein, Bacillus subtilis