Mutational activation of the Cpx signal transduction pathway of Escherichia coli suppresses the toxicity conferred by certain envelope-associated stresses.
The processing-defective outer membrane porin protein LamBA23D (Carlson and Silhavy, 1993) and a tripartite fusion protein, LamB-LacZ-PhoA (Snyder and Silhavy, 1995), are both secreted across the cytoplasmic membrane of Escherichia coli, where they exert an extracytoplasmic toxicity. Suppressors of these toxicities map to a previously characterized gene, cpxA, that encodes the sensor kinase protein of a two-component regulatory system. These activated cpxA alleles, designated as cpxA*, stimulate transcription of the periplasmic protease DegP (Danese et al., 1995), which in turn catalyses degradation of the tripartite fusion protein. In contrast, degradation of precursor LamBA23D is not significantly stimulated in a cpxA* suppressor background. In fact, increased levels of DegP in a wild-type background stabilized this protein. While a functional degP gene is required for full cpxA*-mediated suppression of both toxic envelope proteins, residual suppression is seen in cpxA* degP::Tn10 double mutants. Furthermore, cpxA* mutations suppress the toxicity conferred by the LamB-LacZ hybrid protein, which exerts its effects in the cytoplasm, sequestered from DegP. Together, these observations suggest that the activated Cpx pathway regulates additional downstream targets that contribute to suppression. A subset of these targets may constitute a regulon involved in relieving extracytoplasmic and/or secretion-related stress.
Cosma
C L
CL
Princeton University, Department of Molecular Biology, Lewis Thomas Laboratory, New Jersey 08544, USA.
Danese
P N
PN
Carlson
J H
JH
Silhavy
T J
TJ
Snyder
W B
WB
D001426:Bacterial Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006360:Heat-Shock Proteins; D007763:Lac Operon; D008565:Membrane Proteins / Q000502:physiology; D009154:Mutation; D033903:Periplasmic Proteins; D010957:Plasmids; D011494:Protein Kinases; D021382:Protein Sorting Signals; D012697:Serine Endopeptidases / Q000235:genetics; D015398:Signal Transduction; D013489:Suppression, Genetic
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; C085044:LamB signal peptide, E coli; D008565:Membrane Proteins; D033903:Periplasmic Proteins; D021382:Protein Sorting Signals; D011494:Protein Kinases; C490475:CpxA protein, E coli; C092472:CpxA protein, bacteria; C061682:DegP protease; D012697:Serine Endopeptidases