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 induced the rapid activation of intracellular PLD activity. The PLD activation induced by BK was blocked by pretreatment of A-431 cells with staurosporine, or by prolonged treatment with phorbol-12-myristate-13-acetate (PMA). PKC inhibitors Ro-31-8220 and bisindolylmaleimide I, showed the same inhibitory effects on the BK-stimulated increase of PLD activity, indicating a role 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 specific for PKC-delta, -alpha and -betaI, respectively, markedly inhibited the PLD activity stimulated by BK. These results indicated that PKC, at least PKC-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.