Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector

Science. 1999 Sep 17;285(5435):1920-3. doi: 10.1126/science.285.5435.1920.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
  • Cell Line
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology*
  • HeLa Cells
  • Humans
  • MAP Kinase Kinase Kinase 1*
  • NF-kappa B / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Virulence
  • Yersinia pseudotuberculosis / genetics
  • Yersinia pseudotuberculosis / metabolism
  • Yersinia pseudotuberculosis / pathogenicity
  • Yersinia pseudotuberculosis / physiology*

Substances

  • Bacterial Proteins
  • Enzyme Inhibitors
  • NF-kappa B
  • Recombinant Fusion Proteins
  • YopP protein, Yersinia
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human