Chapter 12 : Signal Transduction and Cross Regulation in the Escherichia coli Phosphate Regulon by PhoR, CreC, and Acetyl Phosphate

Alternative repression complexes for signal transduction by Pi limitation. Pi control may involve Pi binding only to PstS or to both PstS and a regulatory site, which may be on a different Pst component or on PhoR. A hypothetical regulatory site is indicated by a question mark in parentheses. In repression complex I, the PhoR repressor form is shown as a monomer, which is intended to imply any lower oligomeric form. In repression complex II, the PhoR repressor form is shown as a dimer, which is intended to imply any higher oligomeric form. These complexes are compatible with alternative mechanisms for inter-conversion of the PhoR repressor and activator forms as described in the text.

Mechanisms of detection of environmental Pi.The stoichiometric and regulatory site mechanisms are illustrated. In accordance with either mechanism, the PhoR repressor form may be associated with a repression complex when Pi is in excess. The stoichiometric mechanism may lead to the release of PhoR from those complexes to which no Pi is bound under conditions of Pi limitation. The regulatory site mechanism may lead to a conformational change in PhoR (without its release from a repression complex) due to absence of Pi occupancy of the regulatory site. PhoR is shown as a monomer solely for the purpose of illustration. No particular oligomeric form of PhoR is implied.

Mechanisms for interconversion of PhoRR and PhoRA by environmental Pi. Association-dissociation and conformational change mechanisms are illustrated. PhoRR may prevail when the environmental Pi level is in excess (an environmental Pi level greater than about 4 µM); and PhoRA may prevail under conditions of Pi limitation (an environmental Pi level less than about 4 µM). PhoRR may be a phospho-PhoB (PhoB-P) phosphatase, and PhoRA is a phosphoryl transferase and PhoB kinase. Accordingly, PhoRA may autophosphorylate on a histidine residue and transfer this phosphoryl group to an aspartate residue on PhoB. Although PhoRR and PhoRA are depicted in association with PhoB and PhoB-P, respectively, these associations are likely to be transient. No particular oligomeric form of PhoR is implied, except that PhoRA is probably a dimer or higher oligomer. This is because the mechanism of auto-phosphorylation for the PhoR homologs EnvZ and CheA involves phosphorylation of one subunit by the other subunit ( Yang and Inouye, 1991 , 1993 ; Swanson et al., 1993 ; Wolfe and Stewart, 1993 ). The oligomeric structure(s) of PhoR is unknown.

Pta-AckA pathway for ATP synthesis.

Pathways for Pi incorporation into ATP. AtpIBEFHAGDC, ATP synthase; Gap, glyceraldehyde-3-phosphate dehydrogenase; Pgk, phosphoglycerate kinase; PMF, proton motive force; SucCD, succinyl coenzyme A synthetase.

Multiple controls of PhoB phosphorylation by PhoR, CreC, and acetyl phosphate. A signal for the extracellular (ext) Pi level controls the Pho regulon via the Pst system, PhoU, and the Pi sensor PhoR. A signal for an unknown catabolite (which may be an intermediate of a central pathway of carbon, energy, and Pi metabolism) controls the Pho regulon via a central pathway and the catabolite sensor CreC. A signal for ATP synthesis controls the Pho regulon via the Pta-AckA pathway and acetyl phosphate. PhoR, CreC, and acetyl phosphate, in turn, activate the regulator PhoB by phosphorylation. PhoB has been shown to be directly phosphorylated by acetyl phosphate in vitro (Hiratsu et al., personal communication). Nevertheless, it has not been established whether acetyl phosphate acts directly on PhoB as a phosphoryl donor or indirectly via an unknown sensor in vivo ( Wanner and Wilmes-Riesenberg, 1992 ). The solid arrow symbolizes signal transduction by Pi limitation. The dashed arrows symbolize signal transduction due to (proposed) cross regulation. Adapted from Wanner (1992) .