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Science 26 May 2006:
Vol. 312. no. 5777, pp. 1211 - 1214
DOI: 10.1126/science.1126867
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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

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