In unstressed cells RsbT phosphorylates the RsbRA co-antagonist on T171. (A) Following mild environmental stress, RsbRA-T171-P enhances activity of the RsbT kinase (+ arrow), which phosphorylates the RsbS antagonist on S59. This event correlates with release of RsbT from the complex, and RsbT activation of the RsbU phosphatase by direct protein-protein interaction. RsbX feedback phosphatase subsequently removes phosphate from S59, damping the general stress response. (B) Following strong environmental stress, RsbT additionally phosphorylates RsbRA on T205. We propose that doubly phosphorylated RsbRA no longer functions as a kinase activator (− arrow), limiting the general stress response. RsbX phosphatase then removes the phosphate from both RsbRA-T205 and RsbS-S59, resetting the system to function anew in unstressed cells.