Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 26 May 2006:
Vol. 312. no. 5777, pp. 1211 - 1214
DOI: 10.1126/science.1126867
Prev | Table of Contents | Next

Reports

Yersinia YopJ Acetylates and Inhibits Kinase Activation by Blocking Phosphorylation

Sohini Mukherjee,1 Gladys Keitany,1 Yan Li,2,3 Yong Wang,1 Haydn L. Ball,2,3 Elizabeth J. Goldsmith,3 Kim Orth1*

Yersinia species use a variety of type III effector proteins to target eukaryotic signaling systems. The effector YopJ inhibits mitogen-activated protein kinase (MAPK) and the nuclear factor {kappa}B (NF{kappa}B) signaling pathways used in innate immune response by preventing activation of the family of MAPK kinases (MAPKK). We show that YopJ acted as an acetyltransferase, using acetyl–coenzyme A (CoA) to modify the critical serine and threonine residues in the activation loop of MAPKK6 and thereby blocking phosphorylation. The acetylation on MAPKK6 directly competed with phosphorylation, preventing activation of the modified protein. This covalent modification may be used as a general regulatory mechanism in biological signaling.

1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
2 Protein Chemistry Technology Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

* To whom correspondence should be addressed. E-mail: Kim.Orth{at}utsouthwestern.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Recombinant YopJ induces apoptosis in murine peritoneal macrophages in vitro: involvement of mitochondrial death pathway.
A. K. Pandey and A. Sodhi (2009)
Int. Immunol. 21, 1239-1249
   Abstract »    Full Text »    PDF »
Enterohaemorrhagic Escherichia coli serogroup O111 inhibits NF-{kappa}B-dependent innate responses in a manner independent of a type III secreted OspG orthologue.
R. Nobe, J.-P. Nougayrede, F. Taieb, M. Bardiau, D. Cassart, F. Navarro-Garcia, J. Mainil, T. Hayashi, and E. Oswald (2009)
Microbiology 155, 3214-3225
   Abstract »    Full Text »    PDF »
The Activities of the Yersinia Protein Kinase A (YpkA) and Outer Protein J (YopJ) Virulence Factors Converge on an eIF2{alpha} Kinase.
D. J. Wiley, N. Shrestha, J. Yang, N. Atis, K. Dayton, and K. Schesser (2009)
J. Biol. Chem. 284, 24744-24753
   Abstract »    Full Text »    PDF »
A Legionella type IV effector activates the NF-{kappa}B pathway by phosphorylating the I{kappa}B family of inhibitors.
J. Ge, H. Xu, T. Li, Y. Zhou, Z. Zhang, S. Li, L. Liu, and F. Shao (2009)
PNAS 106, 13725-13730
   Abstract »    Full Text »    PDF »
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses.
T. H. Mogensen (2009)
Clin. Microbiol. Rev. 22, 240-273
   Abstract »    Full Text »    PDF »
Burkholderia mallei tssM Encodes a Putative Deubiquitinase That Is Secreted and Expressed inside Infected RAW 264.7 Murine Macrophages.
J. Shanks, M. N. Burtnick, P. J. Brett, D. M. Waag, K. B. Spurgers, W. J. Ribot, M. A. Schell, R. G. Panchal, F. C. Gherardini, K. D. Wilkinson, et al. (2009)
Infect. Immun. 77, 1636-1648
   Abstract »    Full Text »    PDF »
A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle.
Q. Yao, J. Cui, Y. Zhu, G. Wang, L. Hu, C. Long, R. Cao, X. Liu, N. Huang, S. Chen, et al. (2009)
PNAS 106, 3716-3721
   Abstract »    Full Text »    PDF »
Y4lO of Rhizobium sp. Strain NGR234 Is a Symbiotic Determinant Required for Symbiosome Differentiation.
F.-J. Yang, L.-L. Cheng, L. Zhang, W.-J. Dai, Z. Liu, N. Yao, Z.-P. Xie, and C. Staehelin (2009)
J. Bacteriol. 191, 735-746
   Abstract »    Full Text »    PDF »
The Yersinia pestis Ail Protein Mediates Binding and Yop Delivery to Host Cells Required for Plague Virulence.
S. Felek and E. S. Krukonis (2009)
Infect. Immun. 77, 825-836
   Abstract »    Full Text »    PDF »
Glucosamine improves cardiac function following trauma-hemorrhage by increased protein O-GlcNAcylation and attenuation of NF-{kappa}B signaling.
L. Zou, S. Yang, V. Champattanachai, S. Hu, I. H. Chaudry, R. B. Marchase, and J. C. Chatham (2009)
Am J Physiol Heart Circ Physiol 296, H515-H523
   Abstract »    Full Text »    PDF »
Toxoplasma gondii Prevents Chromatin Remodeling Initiated by TLR-Triggered Macrophage Activation.
J. Leng, B. A. Butcher, C. E. Egan, D. S. Abi Abdallah, and E. Y. Denkers (2009)
J. Immunol. 182, 489-497
   Abstract »    Full Text »    PDF »
Cross-Tolerization between Nod1 and Nod2 Signaling Results in Reduced Refractoriness to Bacterial Infection in Nod2-Deficient Macrophages.
Y.-G. Kim, J.-H. Park, S. Daignault, K. Fukase, and G. Nunez (2008)
J. Immunol. 181, 4340-4346
   Abstract »    Full Text »    PDF »
Type III Secretion Decreases Bacterial and Host Survival following Phagocytosis of Yersinia pseudotuberculosis by Macrophages.
Y. Zhang, J. Murtha, M. A. Roberts, R. M. Siegel, and J. B. Bliska (2008)
Infect. Immun. 76, 4299-4310
   Abstract »    Full Text »    PDF »
RD19, an Arabidopsis Cysteine Protease Required for RRS1-R-Mediated Resistance, Is Relocalized to the Nucleus by the Ralstonia solanacearum PopP2 Effector.
M. Bernoux, T. Timmers, A. Jauneau, C. Briere, P. J.G.M. de Wit, Y. Marco, and L. Deslandes (2008)
PLANT CELL 20, 2252-2264
   Abstract »    Full Text »    PDF »
Host-Directed Drug Targeting of Factors Hijacked by Pathogens.
A. Schwegmann and F. Brombacher (2008)
Science Signaling 1, re8
   Abstract »    Full Text »    PDF »
YscP and YscU Switch the Substrate Specificity of the Yersinia Type III Secretion System by Regulating Export of the Inner Rod Protein YscI.
S. E. Wood, J. Jin, and S. A. Lloyd (2008)
J. Bacteriol. 190, 4252-4262
   Abstract »    Full Text »    PDF »
In Vitro Activation of the I{kappa}B Kinase Complex by Human T-cell Leukemia Virus Type-1 Tax.
S. Mukherjee, V. S. Negi, G. Keitany, Y. Tanaka, and K. Orth (2008)
J. Biol. Chem. 283, 15127-15133
   Abstract »    Full Text »    PDF »
The HopZ Family of Pseudomonas syringae Type III Effectors Require Myristoylation for Virulence and Avirulence Functions in Arabidopsis thaliana.
J. D. Lewis, W. Abada, W. Ma, D. S. Guttman, and D. Desveaux (2008)
J. Bacteriol. 190, 2880-2891
   Abstract »    Full Text »    PDF »
Acetylation of Conserved Lysines in the Catalytic Core of Cyclin-Dependent Kinase 9 Inhibits Kinase Activity and Regulates Transcription.
A. Sabo, M. Lusic, A. Cereseto, and M. Giacca (2008)
Mol. Cell. Biol. 28, 2201-2212
   Abstract »    Full Text »    PDF »
Salmonella Secreted Factor L Deubiquitinase of Salmonella typhimurium Inhibits NF-{kappa}B, Suppresses I{kappa}B{alpha} Ubiquitination and Modulates Innate Immune Responses.
G. Le Negrate, B. Faustin, K. Welsh, M. Loeffler, M. Krajewska, P. Hasegawa, S. Mukherjee, K. Orth, S. Krajewski, A. Godzik, et al. (2008)
J. Immunol. 180, 5045-5056
   Abstract »    Full Text »    PDF »
Differential roles of Yersinia outer protein P-mediated inhibition of nuclear factor-kappa B in the induction of cell death in dendritic cells and macrophages.
I. Adkins, S. Schulz, S. Borgmann, I. B. Autenrieth, and S. Grobner (2008)
J. Med. Microbiol. 57, 139-144
   Abstract »    Full Text »    PDF »
VopA Inhibits ATP Binding by Acetylating the Catalytic Loop of MAPK Kinases.
J. E. Trosky, Y. Li, S. Mukherjee, G. Keitany, H. Ball, and K. Orth (2007)
J. Biol. Chem. 282, 34299-34305
   Abstract »    Full Text »    PDF »
Type III Secretion Systems and Disease.
B. Coburn, I. Sekirov, and B. B. Finlay (2007)
Clin. Microbiol. Rev. 20, 535-549
   Abstract »    Full Text »    PDF »
Serogroup-Related Escape of Yersinia enterocolitica YopE from Degradation by the Ubiquitin-Proteasome Pathway.
M. Hentschke, K. Trulzsch, J. Heesemann, M. Aepfelbacher, and K. Ruckdeschel (2007)
Infect. Immun. 75, 4423-4431
   Abstract »    Full Text »    PDF »
Salmonella Effector AvrA Regulation of Colonic Epithelial Cell Inflammation by Deubiquitination.
Z. Ye, E. O. Petrof, D. Boone, E. C. Claud, and J. Sun (2007)
Am. J. Pathol. 171, 882-892
   Abstract »    Full Text »    PDF »
Genetic Analysis of SUMOylation in Arabidopsis: Conjugation of SUMO1 and SUMO2 to Nuclear Proteins Is Essential.
S. A. Saracco, M. J. Miller, J. Kurepa, and R. D. Vierstra (2007)
Plant Physiology 145, 119-134
   Abstract »    Full Text »    PDF »
The Large Clostridial Toxins from Clostridium sordellii and C. difficile Repress Glucocorticoid Receptor Activity.
A. S. Tait, M. Dalton, B. Geny, F. D'Agnillo, M. R. Popoff, and E. M. Sternberg (2007)
Infect. Immun. 75, 3935-3940
   Abstract »    Full Text »    PDF »
Growth of Yersinia pseudotuberculosis in Mice Occurs Independently of Toll-Like Receptor 2 Expression and Induction of Interleukin-10.
V. Auerbuch and R. R. Isberg (2007)
Infect. Immun. 75, 3561-3570
   Abstract »    Full Text »    PDF »
The Yersinia Effector Protein YpkA Induces Apoptosis Independently of Actin Depolymerization.
H. Park, K. Teja, J. J. O'Shea, and R. M. Siegel (2007)
J. Immunol. 178, 6426-6434
   Abstract »    Full Text »    PDF »
SseL, a Salmonella deubiquitinase required for macrophage killing and virulence.
A. Rytkonen, J. Poh, J. Garmendia, C. Boyle, A. Thompson, M. Liu, P. Freemont, J. C. D. Hinton, and D. W. Holden (2007)
PNAS 104, 3502-3507
   Abstract »    Full Text »    PDF »
The Phosphothreonine Lyase Activity of a Bacterial Type III Effector Family.
H. Li, H. Xu, Y. Zhou, J. Zhang, C. Long, S. Li, S. Chen, J.-M. Zhou, and F. Shao (2007)
Science 315, 1000-1003
   Abstract »    Full Text »    PDF »
A Conserved Carboxylesterase Is a SUPPRESSOR OF AVRBST-ELICITED RESISTANCE in Arabidopsis.
S. Cunnac, A. Wilson, J. Nuwer, A. Kirik, G. Baranage, and M. B. Mudgett (2007)
PLANT CELL 19, 688-705
   Abstract »    Full Text »    PDF »
From the Academy: Colloquium Review: Unique characteristics of Xanthomonas oryzae pv. oryzae AvrXa21 and implications for plant innate immunity.
S.-W. Lee, S.-W. Han, L. E. Bartley, and P. C. Ronald (2006)
PNAS 103, 18395-18400
   Abstract »    Full Text »    PDF »
Acetylation of MEK2 and I{kappa}B kinase (IKK) activation loop residues by YopJ inhibits signaling.
R. Mittal, S.-Y. Peak-Chew, and H. T. McMahon (2006)
PNAS 103, 18574-18579
   Abstract »    Full Text »    PDF »
An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination.
T. Tobe, S. A. Beatson, H. Taniguchi, H. Abe, C. M. Bailey, A. Fivian, R. Younis, S. Matthews, O. Marches, G. Frankel, et al. (2006)
PNAS 103, 14941-14946
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)