Activation of phospholipase D activity in transforming growth factor-beta-induced cell growth inhibition

ZHOU Bing Hong, Jun Song CHEN, Ming Qiang CHAI, Sheng ZHAO, Jun LIANG, He Hua CHEN, Jian Guo SONG^*

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China

Cells regulate phospholipase D (PLD) activity in response to numerous extracellular signals. Here, we investigated the involvement of PLD activity in transforming growth factor-b (TGF-b₁)-mediated growth inhibition of epithelial cells. TGF-b inhibits the growth of MDCK, Mv1Lu, and A-549 cells. In the presence of 0.4 % butanol, TGF-b induces an increase in the formation of phosphatidylbutanol, a unique product catalyzed by PLD. TGF-b also induces an increase in phosphatidic acid (PA) level in A-549 and MDCK cells. TGF-b induces an increase in the levels of DAG labeled with [³H]-myristic acid in A-549 and MDCK cells but not in Mv1Lu cells. No increase of DAG was observed in cells prelabeled with [³H]-arachidonic acid. The data presented suggest that PLD activation is involved in the TGF-b-induced cell growth inhibition.

Key words: Transforming growth factor-b, phospholiapse D, signaling, phosphatidic acid, diacylglycerol.