Cross-talk suppression between the CpxA-CpxR and EnvZ-OmpR two-component systems in E. coli

Mol Microbiol. 2008 Oct;70(2):494-506. doi: 10.1111/j.1365-2958.2008.06426.x. Epub 2008 Aug 29.


Many bacteria possess large numbers of two-component signalling systems, which are composed of histidine kinase-response regulator pairs. The high level of sequence similarity between some systems raises the possibility of undesired cross-talk between a histidine kinase and a non-cognate response regulator. Although molecular specificity ensures that phospho-transfer occurs primarily between correct partners, even a low level of inappropriate cross-talk could lead to unacceptable levels of noise or interference in signal transduction. To explore mechanisms that provide insulation against such interference, we have examined cross-talk between the histidine kinase CpxA and non-cognate response regulator OmpR in Escherichia coli. Our results show that there are two mechanisms that suppress cross-talk between these two proteins, which depend on the corresponding cognate partners CpxR and EnvZ and on the bifunctional nature of the histidine kinases CpxA and EnvZ. When cross-talk is detectable, we find it is independent of CpxA stimulus. We also show that cross-talk suppression leads to mutational robustness, i.e. it masks the effects of mutations that would otherwise lead to increased cross-talk. The mechanisms that provide insulation against interference described here may be applicable to many other two-component systems.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / metabolism*
  • DNA, Bacterial / metabolism
  • Escherichia coli / physiology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Gene Expression Regulation, Bacterial*
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Multienzyme Complexes / metabolism*
  • Mutation, Missense
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • Trans-Activators / metabolism*


  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • Multienzyme Complexes
  • Recombinant Fusion Proteins
  • Trans-Activators
  • osmolarity response regulator proteins
  • Green Fluorescent Proteins
  • CpxR protein, Bacteria
  • Protein Kinases
  • CpxA protein, E coli
  • envZ protein, E coli