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

• Published in: The Journal of biological chemistry 2004-03, Vol.279 (10), p.9409-9416
• Main Authors: Su, Heng, McClarty, Grant, Dong, Feng, Hatch, Grant M., Pan, Zhixing K., Zhong, Guangming
• Format: Article
• Language: English
• Subjects: Cell Line; Chlamydia; Chlamydia - growth & development; Chlamydia - metabolism; Chlamydia Infections - metabolism; Chlamydia Infections - microbiology; Glycerophospholipids - metabolism; Humans; MAP Kinase Kinase Kinase 1; MAP Kinase Kinase Kinases - metabolism; Mitogen-Activated Protein Kinases - metabolism; Phospholipases A - metabolism; Phospholipases A2; Proto-Oncogene Proteins c-raf - metabolism; Signal Transduction
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M312008200

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.