Phospholipase D2 (PLD2) and the Epidermal Growth Factor Receptor (EGFR): Identification of a Novel Relationship.

Abstract

Phospholipase D2 (PLD2) catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA), a lipid second messenger. PLD2 is postulated to play a role in enhancing tumorigenesis. EL4 cells, derived from a murine lymphoma, present a unique model to elucidate the role of PLD2 in signal transduction since these cells lack endogenous PLD2 mRNA and protein. In order to elucidate PLD2‐mediated signal transduction, PLD2 was stably transfected into EL4‐V7 cells. In the current study, we asked whether the EGFR, which is known to couple with PLD2, might play a role in PLD2‐mediated effects in EL4 cells. 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 of parental cells or cells transfected with inactive PLD2. Inhibitor studies revealed that EGF‐induced proliferation is mediated by the PI3K/Akt pathway in cells expressing active PLD2. Active PLD2 enhances EGF‐induced invasion of cells through Matrigel, as compared to parental cells or cells expressing inactive PLD2. Taken together, the data suggest that PLD2 can act in concert with EGFR to enhance mitogenesis and invasion in lymphoma cells. (Supported by NIH CA094144‐01)