Two accessory components, the universal stress protein UspC and the phosphotransferase BI 2536 system component IIANtr, are known to interact

with KdpD, allowing the modulation of kdpFABC expression under certain physiological conditions. Here, we will discuss the complexity of a ‘simple’ two-component system and its interconnectivity with metabolism and the general stress response. K+ is important for maintenance of turgor (Epstein, 2003) and the intracellular pH (Booth, 1985), activation of different enzymes (Suelter, 1970), gene expression (Sutherland et al., 1986; Giaever et al., 1988), and regulation of several stress responses, for example chaperone Hsp70 activity (Csonka & Hanson, 1991; Palleros et al., 1993). Escherichia coli has at least three K+ uptake systems, the constitutive systems TrkG/TrkH and Kup, and the inducible high-affinity K+ uptake system KdpFABC to

adjust the intracellular K+ concentration (Altendorf & Epstein, 1996; Stumpe et al., 1996; Buurman et al., 2004). KdpFABC serves as an emergency system to scavenge K+ when the other transporters cannot keep up with the cell’s requirement for K+ (Epstein, 1992). The genes encoding the four subunits of KdpFABC are organized in the kdpFABC operon. Adjacent and overlapping with kdpC is the kdpDE operon, encoding two regulatory proteins: the membrane-integrated histidine (sensor) kinase KdpD and the cytoplasmic response regulator KdpE (Altendorf et al., 1994). The KdpD/KdpE system is one of the most distributed histidine kinase/response regulator NVP-LDE225 system in bacteria. Homologue are found in >420 different bacterial and archaeal species; among them are many pathogens [the KdpD domain

(pfam02702) was used as a query to search the NCBI's Conserved Domain Architecture Retrieval Clomifene Tool (CDART) at http://www.ncbi.nlm.nih.gov (Geer et al., 2002)]. Under K+ limitation or high osmolarity imposed by a salt, the histidine kinase KdpD autophosphorylates and transfers the phosphoryl group to the response regulator KdpE (Voelkner et al., 1993). Phosphorylated KdpE exhibits increased affinity for a 23 base pair sequence upstream of the canonical −35 and −10 regions of the kdpFABC promoter and thereby triggers kdpFABC transcription (Sugiura et al., 1992). The enzymatic activities of purified KdpD and KdpE were determined in vitro (Jung et al., 1997). KdpD is the only protein that dephosphorylates phospho-KdpE, and consequently terminates kdpFABC expression (Jung et al., 1997). This review provides new insights into the molecular mechanism of stimulus perception and signaling by the KdpD/KdpE system in E. coli. The nature of the stimulus that is sensed by KdpD has been puzzling for a long time. Epstein and colleagues found that an increase of external osmolarity at a constant K+ concentration, a condition that reduces turgor, induced kdpFABC expression. The induction level correlated with the magnitude of osmotic stress.