RcsC is a membrane-bound protein that is able to sense extracellular changes in temperature, overexpression of membrane protein, and osmolarity [15, 24, 37]. RcsC is a hybrid kinase, contains both an H1 and D1 domain, and is able to transfer phosphoryl groups to the conserved Hpt domain of RcsD [15, 15, 19]. RcsC and RcsD are inner membrane proteins that are involved in the phosphorylation of RcsB in response to environmental signals [1, 15, 38]. Once phosphorylated, the RcsB protein is a positive regulator and it increases the affinity for the specific DNA-binding sites and controls the transcriptional expression of operons [3, 15, 20, 22, 23, 24]. It has been demonstrated that the Rcs phosphorelay system is induced in the absence of cardiolipin, an anionic phospholipid that appears to participate in signaling for biofilm formation [39]. The RcsB/RcsA complex has major affinity for binding sites of which RcsB is only one. The homodimers of RcsB activate transcription, interacting with the RNA polymerase, by overlapping the -35 box of the core promoter; the central position of the binding site is located near bp -41.5 [2, 3, 9, 10, 12, 15]. The formation of heterodimers between RcsB and the RcsA auxiliary protein stabilizes interactions with the distant binding sites [15, 23, 28, 29, 33, 34]. The amount of RcsA protein is limited both by its rapid degradation by two proteases, Lon and ClpYQ, and by its low level of synthesis [15, 18, 25, 26, 27, 40, 41, 42, 43]. RcsB, which belongs to the two-component family, shows a helix-turn-helix motif for interaction with DNA in the C-terminal domain, while the the N-terminal domain is typical of the response regulator [15]. Regulator protein RcsB is a member of the two-component regulatory system RcsC/RcsB [20, 21, 22] It is involved in the activation of colanic acid capsule synthesis (cps) and cell division (ftsZ) genes [3, 20, 22, 23, 24]. The activation of colanic acid production is through the RcsCDB phosphorelay system in response to structural changes in lipopolysaccharide [44] Based on its homology to other regulator proteins in E. coli, it is believed that the RcsB protein is activated through phosphorylation, probably by the sensor protein RcsC [1]. However, direct phosphorylation of RcsB by RcsC has not been shown. The RcsF protein may also be capable of phosphorylating RcsB. Once activated, the RcsB protein is a positive regulator of capsule synthesis and cell division [3, 20, 22, 23, 24]. Regulator protein RcsB complexes with the RcsA protein (forming a heterodimer) for capsule synthesis activation [18, 20, 23]. RcsB activates the fts genes independently (in the form of a homodimer) [36]. RscB forms a heterodimer with MatA, activating transcription of the matoperon (using thematApromoter and regulatory region of uropathogenic E. coli strain CFT073) in a phosphorylation-independent way. However, this has not been demonstrated for E. coli K-12. This heterodimer probably represses motility in E. coli K-12 (T1241 motile strain) [35]. Several residues in the RcsB receptor domain are crucial for forming complexes with other proteins. The phosphorylation is necessary for the stabilization of the active form of RcsB-RcsB and RcsA-RcsB complexes, while BglJ-RcsB and MatA-RcsB complexes are active intrinsically [35]. The crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of a 22-mer (DNA22) and an 18-mer (DNA18) of the flhDC operon have been solved at 3.15 and 3.37 Å resolution, respectively [45]. It was demostrated that RcsB recognizes target DNA sequences, and the same study revealed a unique oligomeric state that allows RcsB to form homo- and heterodimers [45]. RcsB is a member of the LuxR/UhpA protein family. Overproduction causes a drug resistance phenotype and affects transcription of genes involved in drug efflux [46].