Roles for PLD2 in growth factor-mediated signal transduction in EL4 lymphoma cells

作者：Manpreet S. Chahal · 发表于：Washington State University · 年份：2008 · DOI：10.7273/000005959 · 被引用次数：1 · 研究领域：Chemokine receptors and signaling、Cytokine Signaling Pathways and Interactions、Protein Kinase Regulation and GTPase Signaling

Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. Murine lymphoma EL4 cells lacking endogenous PLD2 expression present a unique model to elucidate the role of PLD2 in signal transduction. Stable overexpression of active PLD2 in EL4 cells does not effect basal proliferation, although expression of inactive PLD2 decreases basal proliferation. Active PLD2 leads to increased basal activation of Akt. Overexpression of active PLD2 leads to enhanced migration in response to serum, however a significant decrease in migration occurs in cells expressing inactive PLD2, as compared to parental cells. Active PLD2 enhances invasion in response to serum, while the opposite is observed with inactive PLD2. Both parental EL4 cells and PLD2 transfectants express endogenous epidermal growth factor receptor (EGFR). Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells. EGF stimulates proliferation of EL4 cells expressing active PLD2, but not parental cells or cells expressing inactive PLD2. PLD2 knockdown (via siRNA) reduces EGF-mediated proliferation in C5 cells to control levels. EGF-mediated proliferation and migration in cells expressing active PLD2 is mediated by the PI3K/Akt pathway. EGF-induced invasion is enhanced in cells expressing active PLD2, as compared to parental cells. In order to elucidate genes modulated by PLD2, we used V7 and C5 cells in a microarray experiment. We identified 102 genes d...