Information transfer through reversible, covalent modifications of proteins is a ubiquitous signalling strategy and bacteria make extensive use of phosphorylation and methylation. The signal is not so much the modification itself but the functional consequences to the target protein that the modification produces. Modifications of bacterial signalling proteins modulate their binding contacts, either with another protein, or between their own domains and subunits.

A large number of proteins belonging to the histidine protein kinase response regulator family have been reported in both Gram negative and Gram positive bacteria. The signalling system in Gram positive bacteria differs from that in Gram negative bacteria in that a peptide pheromone functions as the communication signal and is likely to be directly sensed by the sensor component with subsequent triggering of both the production of the pheromone and the phenotypic change.

In both cases, however, signalling modifications induce a conformational change in the protein. The nature of this change, how it is triggered by the modification, and how this alters functionality are important questions which are still to be resolved.