Bradykinin activates phospholipase D2 via protein kinase cdelta in PC12 cells

Bradykinin (BK) activates phospholipase D (PLD) and induces several responses such as catecholamine secretion, collapse of growth cones, and gene expression in PC12 pheochromocytoma cells. Although two distinct PLD isozymes, PLD1 and PLD2, have been cloned from mammalian cells, the regulatory mechanism for each PLD isozyme by BK is not clear. In our present study, we investigated the activation mechanism of PLD2 by BK in PLD2-overexpressing PC12 cells. BK stimulated PLD2 activity in a concentration-dependent manner within 1 min and this activation was inhibited by pretreatment of the cells with protein kinase C (PKC) inhibitor. PKCalpha and PKCdelta translocated from cytosol to membrane upon BK treatment, and rottlerin potently inhibited the activation of PLD2 by BK. These results suggest that BK activates PLD2 via PKCdelta in PC12 cells.