The Complex Rcs Regulatory Cascade

RcsB, a response regulator of the FixJ/NarL family, is at the center of a complex network of regulatory inputs and outputs. Cell surface stress is sensed by an outer membrane lipoprotein, RcsF, which regulates interactions of the inner membrane protein IgaA, lifting negative regulation of a phosphorelay. In vivo evidence supports a pathway in which histidine kinase RcsC transfers phosphate to phosphotransfer protein RcsD, resulting in phosphorylation of RcsB. RcsB acts either alone or in combination with RcsA to positively regulate capsule synthesis and synthesis of small RNA (sRNA) RprA as well as other genes, and to negatively regulate motility. RcsB in combination with other FixJ/NarL auxiliary proteins regulates yet other functions, independent of RcsB phosphorylation. Proper expression of Rcs and its targets is critical for success of Escherichia coli commensal strains, for proper development of biofilm, and for virulence in some pathogens. New understanding of how the Rcs phosphorelay works provides insight into the flexibility of the two-component system paradigm.