Cellular and molecular action of the mitogenic protein-deamidating toxin from Pasteurella multocida

Brenda A. Wilson, Mengfei Ho

Research output: Contribution to journalReview article

Abstract

The mitogenic toxin from Pasteurella multocida (PMT) is a member of the dermonecrotic toxin family, which includes toxins from Bordetella, Escherichia coli and Yersinia. Members of the dermonecrotic toxin family modulate G-protein targets in host cells through selective deamidation and/or transglutamination of a critical active site Gln residue in the G-protein target, which results in the activation of intrinsic GTPase activity. Structural and biochemical data point to the uniqueness of PMT among these toxins in its structure and action. Whereas the other dermonecrotic toxins act on small Rho GTPases, PMT acts on the α subunits of heterotrimeric G q-, G i- and G 12/13-protein families. To date, experimental evidence supports a model in which PMT potently stimulates various mitogenic and survival pathways through the activation of G q and G 12/13 signaling, ultimately leading to cellular proliferation, whilst strongly inhibiting pathways involved in cellular differentiation through the activation of G i signaling. The resulting cellular outcomes account for the global physiological effects observed during infection with toxinogenic P. multocida, and hint at potential long-term sequelae that may result from PMT exposure. Pasteurella multocida toxin (PMT), a member of the dermonecrotic toxin family that includes toxins from Bordetella, Escherichia coli and Yersinia, stimulates host cell mitogenic and survival pathways, while inhibiting pathways involved in cellular differentiation. Structural and biochemical studies demonstrate that PMT modulates these signaling pathways through deamidation of a critical active site glutamine residue in its heterotrimeric G-protein targets

Original languageEnglish (US)
Pages (from-to)4616-4632
Number of pages17
JournalFEBS Journal
Volume278
Issue number23
DOIs
StatePublished - Dec 1 2011

Keywords

  • G protein
  • adipogenesis
  • atrophic rhinitis
  • deamidation
  • dermonecrotic toxin
  • membrane translocation
  • mitogenesis
  • osteogenesis
  • receptor-mediated endocytosis
  • transglutamination

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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