Bradykinin (BK) activates phospholipase D (PLD) and induces several respons
es such as catecholamine secretion, collapse of growth cones, and gene expr
ession in PC12 pheochromocytoma cells. Although two distinct PLD isozymes,
PLD1 and PLD2, have been cloned from mammalian cells, the regulatory mechan
ism for each PLD isozyme by BK is not clear, In our present study, we inves
tigated the activation mechanism of PLD2 by BK in PLD2-overexpressing PC12
cells. BK stimulated PLD2 activity in a concentration-dependent manner with
in 1 min and this activation was inhibited by pretreatment of the cells wit
h protein kinase C (PKC) inhibitor. PKC alpha and PKC delta translocated fr
om cytosol to membrane upon BK treatment, and rottlerin potently inhibited
the activation of PLD2 by BK. These results suggest that BK activates PLD2
via PKC delta in PC12 cells. (C) 2000 Published by Elsevier Science Ireland
Ltd.