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. 1997 Apr 1;16(7):1670–1685. doi: 10.1093/emboj/16.7.1670

Signal transduction pathways in response to protein misfolding in the extracytoplasmic compartments of E. coli: role of two new phosphoprotein phosphatases PrpA and PrpB.

D Missiakas 1, S Raina 1
PMCID: PMC1169771  PMID: 9130712

Abstract

It is now well established that the sigmaE regulon of Escherichia coli is induced by misfolding of proteins in the periplasm and the outer membrane. htrA belongs to this regulon and encodes a periplasmic protease involved in the degradation of misfolded proteins. htrA transcription is also under the positive control of a two component signal transduction system CpxR CpxA. Closer examination of the putative signal transduction pathway modulating htrA transcription has led us to the identification of two new genes. Biochemical and genetic evidence shows that these two genes encode two phosphoprotein phosphatases, designated PrpA and PrpB. These are the first examples of typical serine/threonine and tyrosine phosphatases described in E. coli. PrpA and PrpB are involved in signaling protein misfolding via the CpxR CpxA transducing system. In addition, both PrpA and PrpB modulate the phosphorylated status of some other phosphoproteins in E. coli. Finally, we show that PrpA is a heat shock protein.

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Selected References

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  1. Aiba H., Nakasai F., Mizushima S., Mizuno T. Evidence for the physiological importance of the phosphotransfer between the two regulatory components, EnvZ and OmpR, in osmoregulation in Escherichia coli. J Biol Chem. 1989 Aug 25;264(24):14090–14094. [PubMed] [Google Scholar]
  2. Barik S. Expression and biochemical properties of a protein serine/threonine phosphatase encoded by bacteriophage lambda. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10633–10637. doi: 10.1073/pnas.90.22.10633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barker H. M., Jones T. A., da Cruz e Silva E. F., Spurr N. K., Sheer D., Cohen P. T. Localization of the gene encoding a type I protein phosphatase catalytic subunit to human chromosome band 11q13. Genomics. 1990 Jun;7(2):159–166. doi: 10.1016/0888-7543(90)90536-4. [DOI] [PubMed] [Google Scholar]
  4. Cohen P. T., Cohen P. Discovery of a protein phosphatase activity encoded in the genome of bacteriophage lambda. Probable identity with open reading frame 221. Biochem J. 1989 Jun 15;260(3):931–934. doi: 10.1042/bj2600931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen P. T., Collins J. F., Coulson A. F., Berndt N., da Cruz e Silva O. B. Segments of bacteriophage lambda (orf 221) and phi 80 are homologous to genes coding for mammalian protein phosphatases. Gene. 1988 Sep 15;69(1):131–134. doi: 10.1016/0378-1119(88)90385-x. [DOI] [PubMed] [Google Scholar]
  6. Cosma C. L., Danese P. N., Carlson J. H., Silhavy T. J., Snyder W. B. Mutational activation of the Cpx signal transduction pathway of Escherichia coli suppresses the toxicity conferred by certain envelope-associated stresses. Mol Microbiol. 1995 Nov;18(3):491–505. doi: 10.1111/j.1365-2958.1995.mmi_18030491.x. [DOI] [PubMed] [Google Scholar]
  7. Cox J. S., Shamu C. E., Walter P. Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase. Cell. 1993 Jun 18;73(6):1197–1206. doi: 10.1016/0092-8674(93)90648-a. [DOI] [PubMed] [Google Scholar]
  8. Danese P. N., Snyder W. B., Cosma C. L., Davis L. J., Silhavy T. J. The Cpx two-component signal transduction pathway of Escherichia coli regulates transcription of the gene specifying the stress-inducible periplasmic protease, DegP. Genes Dev. 1995 Feb 15;9(4):387–398. doi: 10.1101/gad.9.4.387. [DOI] [PubMed] [Google Scholar]
  9. Dong J., Iuchi S., Kwan H. S., Lu Z., Lin E. C. The deduced amino-acid sequence of the cloned cpxR gene suggests the protein is the cognate regulator for the membrane sensor, CpxA, in a two-component signal transduction system of Escherichia coli. Gene. 1993 Dec 22;136(1-2):227–230. doi: 10.1016/0378-1119(93)90469-j. [DOI] [PubMed] [Google Scholar]
  10. Egloff M. P., Cohen P. T., Reinemer P., Barford D. Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate. J Mol Biol. 1995 Dec 15;254(5):942–959. doi: 10.1006/jmbi.1995.0667. [DOI] [PubMed] [Google Scholar]
  11. Fellay R., Frey J., Krisch H. Interposon mutagenesis of soil and water bacteria: a family of DNA fragments designed for in vitro insertional mutagenesis of gram-negative bacteria. Gene. 1987;52(2-3):147–154. doi: 10.1016/0378-1119(87)90041-2. [DOI] [PubMed] [Google Scholar]
  12. Goldberg J., Huang H. B., Kwon Y. G., Greengard P., Nairn A. C., Kuriyan J. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature. 1995 Aug 31;376(6543):745–753. doi: 10.1038/376745a0. [DOI] [PubMed] [Google Scholar]
  13. Griffith J. P., Kim J. L., Kim E. E., Sintchak M. D., Thomson J. A., Fitzgibbon M. J., Fleming M. A., Caron P. R., Hsiao K., Navia M. A. X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Cell. 1995 Aug 11;82(3):507–522. doi: 10.1016/0092-8674(95)90439-5. [DOI] [PubMed] [Google Scholar]
  14. Missiakas D., Betton J. M., Raina S. New components of protein folding in extracytoplasmic compartments of Escherichia coli SurA, FkpA and Skp/OmpH. Mol Microbiol. 1996 Aug;21(4):871–884. doi: 10.1046/j.1365-2958.1996.561412.x. [DOI] [PubMed] [Google Scholar]
  15. Missiakas D., Schwager F., Betton J. M., Georgopoulos C., Raina S. Identification and characterization of HsIV HsIU (ClpQ ClpY) proteins involved in overall proteolysis of misfolded proteins in Escherichia coli. EMBO J. 1996 Dec 16;15(24):6899–6909. [PMC free article] [PubMed] [Google Scholar]
  16. Missiakas D., Schwager F., Raina S. Identification and characterization of a new disulfide isomerase-like protein (DsbD) in Escherichia coli. EMBO J. 1995 Jul 17;14(14):3415–3424. doi: 10.1002/j.1460-2075.1995.tb07347.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mori K., Ma W., Gething M. J., Sambrook J. A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus. Cell. 1993 Aug 27;74(4):743–756. doi: 10.1016/0092-8674(93)90521-q. [DOI] [PubMed] [Google Scholar]
  18. Parkinson J. S. Signal transduction schemes of bacteria. Cell. 1993 Jun 4;73(5):857–871. doi: 10.1016/0092-8674(93)90267-t. [DOI] [PubMed] [Google Scholar]
  19. Perego M., Glaser P., Hoch J. A. Aspartyl-phosphate phosphatases deactivate the response regulator components of the sporulation signal transduction system in Bacillus subtilis. Mol Microbiol. 1996 Mar;19(6):1151–1157. doi: 10.1111/j.1365-2958.1996.tb02460.x. [DOI] [PubMed] [Google Scholar]
  20. Raina S., Georgopoulos C. A new Escherichia coli heat shock gene, htrC, whose product is essential for viability only at high temperatures. J Bacteriol. 1990 Jun;172(6):3417–3426. doi: 10.1128/jb.172.6.3417-3426.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raina S., Missiakas D., Georgopoulos C. The rpoE gene encoding the sigma E (sigma 24) heat shock sigma factor of Escherichia coli. EMBO J. 1995 Mar 1;14(5):1043–1055. doi: 10.1002/j.1460-2075.1995.tb07085.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rampersaud A., Harlocker S. L., Inouye M. The OmpR protein of Escherichia coli binds to sites in the ompF promoter region in a hierarchical manner determined by its degree of phosphorylation. J Biol Chem. 1994 Apr 29;269(17):12559–12566. [PubMed] [Google Scholar]
  23. Rouvière P. E., De Las Peñas A., Mecsas J., Lu C. Z., Rudd K. E., Gross C. A. rpoE, the gene encoding the second heat-shock sigma factor, sigma E, in Escherichia coli. EMBO J. 1995 Mar 1;14(5):1032–1042. doi: 10.1002/j.1460-2075.1995.tb07084.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sherman MYu, Goldberg A. L. Heat shock in Escherichia coli alters the protein-binding properties of the chaperonin groEL by inducing its phosphorylation. Nature. 1992 May 14;357(6374):167–169. doi: 10.1038/357167a0. [DOI] [PubMed] [Google Scholar]
  25. Singer M., Baker T. A., Schnitzler G., Deischel S. M., Goel M., Dove W., Jaacks K. J., Grossman A. D., Erickson J. W., Gross C. A. A collection of strains containing genetically linked alternating antibiotic resistance elements for genetic mapping of Escherichia coli. Microbiol Rev. 1989 Mar;53(1):1–24. doi: 10.1128/mr.53.1.1-24.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Slater S., Maurer R. Simple phagemid-based system for generating allele replacements in Escherichia coli. J Bacteriol. 1993 Jul;175(13):4260–4262. doi: 10.1128/jb.175.13.4260-4262.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Weber R. F., Silverman P. M. The cpx proteins of Escherichia coli K12. Structure of the cpxA polypeptide as an inner membrane component. J Mol Biol. 1988 Sep 20;203(2):467–478. doi: 10.1016/0022-2836(88)90013-7. [DOI] [PubMed] [Google Scholar]
  28. Weiner L., Brissette J. L., Model P. Stress-induced expression of the Escherichia coli phage shock protein operon is dependent on sigma 54 and modulated by positive and negative feedback mechanisms. Genes Dev. 1991 Oct;5(10):1912–1923. doi: 10.1101/gad.5.10.1912. [DOI] [PubMed] [Google Scholar]
  29. Zhuo S., Clemens J. C., Hakes D. J., Barford D., Dixon J. E. Expression, purification, crystallization, and biochemical characterization of a recombinant protein phosphatase. J Biol Chem. 1993 Aug 25;268(24):17754–17761. [PubMed] [Google Scholar]

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