Extracellular signal-regulated kinase activation by Neisseria gonorrhoeae downregulates epithelial cell proapoptotic proteins Bad and Bim

Heather L. Howie, Shelly L. Shiflett, Magdalene "Maggie" So

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Neisseria gonorrhoeae expressing type IV pili (Tfp) activates extracellular signal-regulated kinase (ERK) and induces a cytoprotective state in the epithelial cell in a manner that is enhanced by pilT. As the ERK signaling pathway is well-known for its role in cytoprotection and cell survival, we tested the hypothesis that ERK is involved in producing this cytoprotective effect. Inhibiting ERK activation prior to infection attenuated the ability of these bacteria to induce cytoprotection. Activated ERK specifically targeted two proapoptotic Bcl-2 homology domain 3 (BH3)-only proteins, Bim and Bad, for downregulation at the protein level. Bim downregulation occurred through the proteasome. ERK, in addition, inactivated Bad by triggering its phosphorylation at Ser112. Finally, reducing the level of either Bad or Bim alone by small interfering RNA was sufficient to protect uninfected cells from staurosporine-induced apoptosis. We conclude that Tfp-induced cytoprotection is due in part to ERK-dependent modification and/or downregulation of proapoptotic proteins Bad and Bim.

Original languageEnglish (US)
Pages (from-to)2715-2721
Number of pages7
JournalInfection and Immunity
Volume76
Issue number6
DOIs
StatePublished - Jun 2008

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bcl-Associated Death Protein
Neisseria gonorrhoeae
Extracellular Signal-Regulated MAP Kinases
Down-Regulation
Epithelial Cells
Cytoprotection
Staurosporine
Proteasome Endopeptidase Complex
Small Interfering RNA
Cell Survival
Phosphorylation
Apoptosis
Bacteria

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Extracellular signal-regulated kinase activation by Neisseria gonorrhoeae downregulates epithelial cell proapoptotic proteins Bad and Bim. / Howie, Heather L.; Shiflett, Shelly L.; So, Magdalene "Maggie".

In: Infection and Immunity, Vol. 76, No. 6, 06.2008, p. 2715-2721.

Research output: Contribution to journalArticle

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