Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector.
The bacterial pathogen Yersinia uses a type III secretion system to inject several virulence factors into target cells. One of the Yersinia virulence factors, YopJ, was shown to bind directly to the superfamily of MAPK (mitogen-activated protein kinase) kinases (MKKs) blocking both phosphorylation and subsequent activation of the MKKs. These results explain the diverse activities of YopJ in inhibiting the extracellular signal-regulated kinase, c-Jun amino-terminal kinase, p38, and nuclear factor kappa B signaling pathways, preventing cytokine synthesis and promoting apoptosis. YopJ-related proteins that are found in a number of bacterial pathogens of animals and plants may function to block MKKs so that host signaling responses can be modulated upon infection.
Orth
K
K
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-0606, USA.
Palmer
L E
LE
Bao
Z Q
ZQ
Stewart
S
S
Rudolph
A E
AE
Bliska
J B
JB
Dixon
J E
JE
D001426:Bacterial Proteins / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014774:Virulence; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; C109227:YopP protein, Yersinia; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human