Literature DB >> 17419997

PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis.

Lingfeng Chen1, Miho Iijima, Ming Tang, Mark A Landree, Yi Elaine Huang, Yuan Xiong, Pablo A Iglesias, Peter N Devreotes.   

Abstract

Directed cell migration involves signaling events that lead to local accumulation of PI(3,4,5)P(3), 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 A(2). Loss of this gene did not alter PI(3,4,5)P(3) regulation, but chemotaxis became sensitive to reductions in PI3K activity. Likewise, cells deficient in PI3K activity were more sensitive to inhibition of PLA(2) activity. Deletion of the PLA(2) 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 PLA(2) homolog, and exogenous arachidonic acid reduced their dependence on PI3K signaling. We propose that PLA(2) and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA(2) may be important mediators of the response.

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Year:  2007        PMID: 17419997      PMCID: PMC1986835          DOI: 10.1016/j.devcel.2007.03.005

Source DB:  PubMed          Journal:  Dev Cell        ISSN: 1534-5807            Impact factor:   12.270


  55 in total

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  106 in total

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10.  From Physics to Pharmacology?

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