Signaling in ECF activation takes an interesting variety of forms. In this review, we have discussed the two major groups of signaling mechanisms represented by the σE and the FecI signaling. Some of the associations with these groups are based on what appear to be somewhat similar mechanisms rather than homology, like the association of CarQ signaling with σE signaling. Although the components of the CarQ signaling pathway have no homology to the components of the σE signaling pathway, the evidence that activation of CarQ is concomitant with anti-sigma factor degradation suggests a mechanism similar to that of the regulation of σE. Most other systems of ECF regulation, especially in Gram-negative bacteria, appear to have components that are homologous to components of either the σE or the FecI signaling systems. However, these components are often not used identically and illustrate the great diversity of the use of the components of the signaling systems.
Comparison of the σE-like and the FecI-like signaling systems suggests that one simple explanation for some of their differences is that these systems communicate conditions from different cellular locations. The FecARI system signals the presence of extracellular iron-citrate through two membranes and the intervening periplasmic space. The FecARI model of signaling is appropriate for signaling the presence of small molecules that only reach the periplasm by transport, such as chelated iron in the case of FecARI. The two-component, Cpx-like and the RIP protease, σE-like systems that recognize periplasmic stimuli could possibly be used for signaling. However, as periplasmic detection of the extracellular molecules would first require transport, this method of detection and signaling would not be as efficient as the FecARI-like system. This is especially the case for the PrhARI signaling system from Ralstonia solanacearum, because this system detects an integral part of an intact plant cell wall which can not enter into the periplasm.
-like activation pathway is appropriate for recognition of periplasmic stimuli in Gram-negative bacteria or external stimuli in Gram-positive bacteria. Because the detection of the periplasmic stimuli of σE
could be detected by a two-component signaling system such as Cpx, activation of many of the regulons with the σE
-like pathway may alternatively be regulated by a two-component signaling pathway. It is not clear what pressures determine why a regulon would be controlled by one or the other, thus an interchangeability of these signaling systems is suggested. This is partly reflected by a σE
homologue in the Gram-positive bacterium Streptomyces coelicolor
A3(2), which appears to be regulated by a two-component system [18
]. Although Gram-positive bacteria do not have a periplasm, σE
-like RIP protease mechanisms appear to play a role in regulation of ECF sigma factors in these organisms as well. The σW
signaling system from B. subtilis
contains an anti-sigma factor and a RIP protease. Given the universality of the RIP protease mechanism, it should be no surprise that ECF signaling systems in Gram-positive bacteria use σE
-like RIP protease mechanisms.
An almost universal commonality to ECF signaling, especially in Gram-negative bacteria, is the use of anti-sigma factors. The two major mechanisms of ECF sigma factor regulation and the variations all use anti-sigma factors. Anti-sigma factors are probably retained for a number of reasons. Two coupled reasons are that the anti-sigma factor protects the sigma factor from degradation and the sigma factor is ready to act as soon as it is activated or released. The use of an anti-sigma factor as a signaling component also lends itself to a variety of regulatory mechanisms which are not limited to those presented in this review [19
Another commonality in signaling in these systems is protein recognition through addition of a β-strand of one protein into a β-sheet in the other. In the ECF signaling mechanisms these interactions are primarily mediated by PDZ domains. The σE signaling mechanism contains PDZ domain interactions with both DegS-OMP recognition as well as regulation of RseP. The Prc protease that plays a role in the regulation of AlgU in mutant P. aeruginosa also contains a PDZ domain which may play a role in AlgU activity. In the FecARI signaling system, TonB interacts with the TonB box through β-strand addition.
In summary, ECF sigma factor signaling is extremely diverse, most likely in order to address different types of signals from various locations. The signaling mechanisms often use similar components, but in different signaling systems these components can be used in different ways.