Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation.
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.
Mukherjee
Sohini
S
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Keitany
Gladys
G
Li
Yan
Y
Wang
Yong
Y
Ball
Haydn L
HL
Goldsmith
Elizabeth J
EJ
Orth
Kim
K
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
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