Activation of Raf/MEK/ERK/cPLA2 Signaling Pathway Is Essential for Chlamydial Acquisition of Host Glycerophospholipids

Heng Su, Grant McClarty, Feng Dong, Grant M. Hatch, Zhixing K. Pan, Guangming Zhong

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Chlamydiae, a diverse group of obligate intracellular pathogens replicating within cytoplasmic vacuoles of eukaryotic cells, are able to acquire lipids from host cells. Here we report that activation of the host Raf-MEK-ERK-cPLA2 signaling cascade is required for the chlamydial uptake of host glycerophospholipids. Both the MAP kinase pathway (Ras/Raf/MEK/ERK) and Ca2+-dependent cytosolic phospholipase A2 (cPLA2) were activated in chlamydia-infected cells. The inhibition of cPLA2 activity resulted in the blockade of the chlamydial uptake of host glycerophospholipids and impairment in chlamydial growth. Blocking either c-Raf-1 or MEK1/2 activity prevented the chlamydial activation of ERK1/2, leading to the suppression of both chlamydial activation of the host cPLA2 and uptake of glycerophospholipids from the host cells. The chlamydia-induced phosphorylation of cPLA2 was also blocked by a dominant negative ERK2. Furthermore, activation of both ERK1/2 and cPLA2 was dependent on chlamydial growth and restricted within chlamydia-infected cells, suggesting an active manipulation of the host ERK-cPLA2 signaling pathway by chlamydiae.

Original languageEnglish (US)
Pages (from-to)9409-9416
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number10
DOIs
StatePublished - Mar 5 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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