Functional crosstalk between phospholipase D2 and signaling phospholipase A2/cyclooxygenase-2-mediated prostaglandin biosynthetic pathways

We performed reconstitution analyses of functional interaction between phospholipase A2 (PLA2) and phospholipase D (PLD) enzymes. Cotransfection of HEK293 cells with cytosolic (cPLA2) or type IIA secretory (sPLA2-IIA) PLA2 and PLD2, but not PLD1, led to marked augmentation of stimulus-induced arachidonate release. Interleukin-1-stimulated arachidonate release was accompanied by prostaglandin E2 production via cyclooxygenase-2, the expression of which was augmented by PLD2. Conversely, activation of PLD2, not PLD1, was facilitated by cPLA2 or sPLA2-IIA. Thus, our results revealed functional crosstalk between signaling PLA2s and PLD2 in the regulation of various cellular responses in which these enzymes have been implicated.