PLA2 and PI3K/PTEN Pathways Act in Parallel to Mediate Chemotaxis

Lingfeng Chen, Miho Iijima, Ming Tang, Mark A. Landree, Yi Elaine Huang, Yuan Xiong, Pablo A. Iglesias, Peter N. Devreotes

Research output: Contribution to journalArticlepeer-review

Abstract

Directed cell migration involves signaling events that lead to local accumulation of PI(3,4,5)P3, but additional pathways act in parallel. A genetic screen in Dictyostelium discoideum to identify redundant pathways revealed a gene with homology to patatin-like phospholipase A2. Loss of this gene did not alter PI(3,4,5)P3 regulation, but chemotaxis became sensitive to reductions in PI3K activity. Likewise, cells deficient in PI3K activity were more sensitive to inhibition of PLA2 activity. Deletion of the PLA2 homolog and two PI3Ks caused a strong defect in chemotaxis and a reduction in receptor-mediated actin polymerization. In wild-type cells, chemoattractants stimulated a rapid burst in an arachidonic acid derivative. This response was absent in cells lacking the PLA2 homolog, and exogenous arachidonic acid reduced their dependence on PI3K signaling. We propose that PLA2 and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA2 may be important mediators of the response.

Original languageEnglish (US)
Pages (from-to)603-614
Number of pages12
JournalDevelopmental Cell
Volume12
Issue number4
DOIs
StatePublished - Apr 2007

Keywords

  • CELLBIO
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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