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Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, Washington, WA 99164-6534, USA
Program in Nutrition and Exercise Physiology, College of Pharmacy, Washington State University, Spokane, Washington, WA99210-1495, USA
* Author to whom correspondence should be addressed.
Received: 23 April 2010; in revised form: 24 May 2010 / Accepted: 24 June 2001 / Published: 2 July 2010
Abstract: Phospholipase D2 (PLD2) generates phosphatidic acid through hydrolysis of phosphatidylcholine. PLD2 has been shown to play a role in enhancing tumorigenesis. The epidermal growth factor receptor (EGFR) can both activate and interact with PLD2. Murine lymphoma EL4 cells lacking endogenous PLD2 present a unique model to elucidate the role of PLD2 in signal transduction. In the current study, we investigated effects of PLD2 on EGF response. Western blotting and RT-PCR were used to establish that both parental cells and PLD2 transfectants express endogenous EGFR. Levels of EGFR protein are increased in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. EGF stimulates proliferation of EL4 cells transfected with active PLD2, but not parental cells or cells transfected with inactive PLD2. EGF-mediated proliferation in cells expressing active PLD2 is dependent on the activities of both the EGFR and the PI3K/Akt pathway, as demonstrated by studies using protein kinase inhibitors. EGF-induced invasion through a synthetic extracellular matrix is enhanced in cells expressing active PLD2, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 acts in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells.
Keywords: protein kinase inhibitors; phospholipids metabolism; metastasis
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Chahal, M.S.; Brauner, D.J.; Meier, K.E. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells. Pharmaceuticals 2010, 3, 2045-2058.
Chahal MS, Brauner DJ, Meier KE. Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells. Pharmaceuticals. 2010; 3(7):2045-2058.
Chahal, Manpreet S.; Brauner, Daniel J.; Meier, Kathryn E. 2010. "Phospholipase D2 Enhances Epidermal Growth Factor-Induced Akt Activation in EL4 Lymphoma Cells." Pharmaceuticals 3, no. 7: 2045-2058.