PKCδ inhibits PKCα‐mediated activation of phospholipase D1 in a manner independent of its protein kinase activity

摘要

>The regulation of phospholipase D1 (PLD1) by protein kinase C (PKC) isoforms was analyzed in human melanoma cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced PLD1 activation was suppressed by the introduction of PKCδ as well as its kinase-negative mutant in MeWo cells, which contain PKCα but lack PKCβ. PLD activity was not affected by PKCδ in G361 cells, which have PKCβ but are deficient in PKCα. In MeWo cells introduced by PKCα and PLD1, the association of these proteins was observed, which was enhanced by the TPA treatment. In cells overexpressing PKCδ in addition to PKCα and PLD1, TPA treatment increased the association of PKCδ and PLD1, while it attenuated the association of PKCα and PLD1. These results indicate that PKCδ inhibits TPA-induced PLD1 activation mediated by PKCα through the association with PLD1.