title: Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation.
abstract: 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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Sohini
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Gladys
authors.initials: G
authors.lastname: Keitany
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Haydn L
authors.initials: HL
authors.lastname: Ball
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Goldsmith
authors.forename: Kim
authors.initials: K
authors.lastname: Orth
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D020134:Catalytic Domain; D002460:Cell Line; D002474:Cell-Free System; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D048669:MAP Kinase Kinase 6 / Q000737:chemistry / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D015007:Yersinia / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; C109227:YopP protein, Yersinia; D013912:Threonine; D012694:Serine; D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048669:MAP Kinase Kinase 6; C482566:MAP2K6 protein, human