The molecular basis of phospholipase D2-induced chemotaxis: elucidation of differential pathways in macrophages and fibroblasts.

Molecular and Cellular Biology
Katie KnapekJulian Gomez-Cambronero

Abstract

We report the molecular mechanisms that underlie chemotaxis of macrophages and cell migration of fibroblasts, cells that are essential during the body's innate immune response and during wound repair, respectively. Silencing of phospholipase D1 (PLD1) and PLD2 reduced cell migration (both chemokinesis and chemotaxis) by approximately 60% and >80%, respectively; this migration was restored by cell transfection with PLD2 constructs refractory to small interfering RNA (siRNA). Cells overexpressing active phospholipase D1 (PLD1) but, mostly, active PLD2 exhibited cell migration capabilities that were elevated over those elicited by chemoattractants alone. The mechanism for this enhancement is complex. It involves two pathways: one that is dependent on the activity of the lipase (and signals through its product, phosphatidic acid [PA]) and another that involves protein-protein interactions. The first is evidenced by partial abrogation of chemotaxis with lipase activity-defective constructs (PLD2-K758R) and by n-butanol treatment of cells. The second is evidenced by PLD association with the growth factor receptor-bound protein 2 (Grb2) through residue Y(169), located within a Src homology 2 (SH2) consensus site. The association Grb2-...Continue Reading

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Citations

Jun 6, 2013·ACS Applied Materials & Interfaces·Siew P HooZhilian Yue
May 6, 2011·The Journal of Biological Chemistry·Chuanshen WuArie Horowitz
Oct 5, 2012·The Journal of Biological Chemistry·Madhu MahankaliJulian Gomez-Cambronero
Sep 21, 2011·Molecular and Cellular Biology·Samuel KantonenJulian Gomez-Cambronero
Jul 4, 2012·Journal of Leukocyte Biology·Julian Gomez-Cambronero
Feb 14, 2013·The Journal of Biological Chemistry·Qing YeJulian Gomez-Cambronero
Dec 24, 2015·Advances in Biological Regulation·Jaewang GhimSung Ho Ryu
Aug 31, 2014·The International Journal of Biochemistry & Cell Biology·Melina V MateosGabriela A Salvador
Aug 2, 2014·Journal of Leukocyte Biology·Julian Gomez-Cambronero, Samuel Kantonen
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Jul 6, 2014·The Journal of Biological Chemistry·Julian Gomez-Cambronero
Dec 13, 2019·Progress in Lipid Research·M I McDermottV A Bankaitis
Apr 10, 2021·Cell Communication and Signaling : CCS·Helena M StrickerThomas Dittmar
Mar 2, 2011·Archives of Biochemistry and Biophysics·Haein ParkDianne Cox

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