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 gove rned by a signal transduction network that regulates activity of the s igma(B) transcription factor. We show that this network comprises two partner-switching modules, RsbX-RsbS-RsbT and RsbU-RsbV-RsbW, which co ntribute 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 pr imary regulator of sigma(B) activity. If the V antagonist is phosphory lated, the W switch protein binds and inhibits sigma(B). If V is unpho sphorylated, it complexes W, freeing sigma(B) to interact with RNA pol ymerase and promote transcription. The phosphorylation state of V is c ontrolled 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 interacti on is governed by the phosphorylation state of the S antagonist, contr olled by opposing kinase (T) and phosphatase (X) activities. This part ner-switching mechanism provides a general regulatory strategy in whic h Linked modules sense and integrate multiple signals by protein-prote in interaction.