Although oleate has been implicated in the regulation of phospholipase D (P
LD) activity, the molecular identity of the oleate-stimulated PLD is still
poorly understood. We now report that oleate selectively stimulates the enz
ymatic activity of PLD2 but not of PLD1, with an optimal concentration of 2
0 mu M in vitro. Intriguingly, phosphatidylinositol 4,5-bisphosphate (PIP2)
synergistically stimulates the oleate-dependent PLD2 activity with an opti
mal concentration of 2.5 mu M. These results provide the first evidence tha
t oleate is a PLD2-specific activating factor and PLD2 activity is synergis
tically stimulated by oleate and PIP2, (C) 1999 Federation of European Bioc
hemical Societies.