Enhancement of lysophosphatidic acid-induced ERK phosphorylation by phospholipase D1 via the formation of phosphatidic acid

We made stable cell lines overexpressing PLD1 (GP-PLD1) from GP+envAm12 cel l, a derivative of NIH 3T3 cell. PLD1 activity and extracellular signal-reg ulated kinase (ERR) phosphorylation were enhanced in GP-PLD1 cells by the t reatment of lysophosphatidic acid (LPA). In contrast, these LPA-induced eff ects were attenuated with the pretreatment of pertussis toxin (PTX) or prot ein kinase C (PKC) inhibitor. Moreover, accumulation of phosphatidic acid ( PA), a product of PLD action, potentiated the LPA-induced ERR activation in GP-PLD1 cells while blocking of PA production with the treatment of 1-buta nol attenuated LPA-induced ERK phosphorylation. From these results, we sugg est that LPA activate PLD1 through pertussis toxin-sensitive G protein and PKC dependent pathways, then PA produced from PLD1 activation facilitate ER R phosphorylation. (C) 2001 Academic Press.