Effects of Active and Inactive Phospholipase D2 on Signal Transduction, Adhesion, Migration, Invasion,

The phosphatidylcholine-using phospholipase D (PLD) iso-form PLD2 is widely expressed in mammalian cells and is activated in response to a variety of promitogenic agonists. In this study, active and inactive hemagglutinin-tagged human PLD2 (HA-PLD2) constructs were stably expressed in an EL4 cell line lacking detectable endogenous PLD1 or PLD2. The overall goal of the study was to examine the roles of PLD2 in cellular signal transduction and cell phenotype. HA-PLD2 con-fers PLD activity that is activated by phorbol ester, ionomycin, and okadaic acid. Proliferation and Erk activation are un-changed in cells transfected with active PLD2; proliferation rate is decreased in cells expressing inactive PLD2. Basal tyrosine phosphorylation of focal adhesion kinase (FAK) is increased in cells expressing active PLD2, as is phosphorylation of Akt