Yersinia YopJ Acetylates and Inhibits Kinase Activation by Blocking Phosphorylation

作者：Sohini Mukherjee, Gladys J. Keitany, Yan Li, Yong Wang, Haydn L. Ball, Elizabeth J. Goldsmith, Kim Orth · 发表于：Science · 年份：2006 · DOI：10.1126/science.1126867 · 被引用次数：623 · 研究领域：Yersinia bacterium, plague, ectoparasites research、Pharmacological Effects of Natural Compounds、Plant-based Medicinal Research

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 kappaB (NFkappaB) 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.