Bradykinin induces protein kinase C-dependent activation of phospholipase D in A-431 cells

The protein kinase C involvement in bradykinin (BK)-induced phospholipase D (PLD) activation in A-431 cells was examined. Treatment of cells with BK i nduced the rapid activation of intracellular PLD activity, The PLD activati on induced by BK was blocked by pretreatment of A-431 cells with staurospor ine, or by prolonged treatment with phorbol-12-myristate-13-acetate (PMA), PKC inhibitors Re-31-8220 and bisindolylmaleimide 1, showed the same inhibi tory effects on the BK-stimulated increase of PLD activity, indicating a ro le of PKC in this activation process, Similar results were observed in PMA- induced PLD activation, In contrast, PKC down-regulation or PKC inhibitors had no obvious effect on the PLD activation stimulated by epidermal growth factor (EGF), Furthermore, rottlerin and Go 6976, the PKC inhibitors specif ic for PKC-delta, -alpha and -betaI, respectively, markedly inhibited the P LD activity stimulated by BK, These results indicated that PKC, at least PK C-delta and Ca2+-dependent PKC-alpha or -betaI, plays an important role in BK-induced but not EGF-induced PLD activation in A-431 cells.