Overexpression of phospholipase D enhances Bcl-2 expression by activating STAT3 through independent activation of ERK and p38MAPK in HeLa cells
- 作者：Hye-Jin Choi ; Joong-Soo Han ; jshan@hanyang.ac.kr
- 关键词：PLD ; phospholipase D ; PA ; phosphatidic acid ; Bcl-2 ; B-cell leukemia/lymphoma 2 ; PLA2 ; phospholipases A ; LPA ; lysophosphatidic acid ; DPPA ; 1 ; 2-dipalmitoyl-sn-glycero-3-phosphate ; MAPK ; mitogen-activated protein kinase ; ERK ; extracellular signal-regulated k
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
- 出版年：2012
- 期刊代码：20_01674889
- 类别：bio
- 出版时间：June, 2012
- 卷：1823
- 期：6
- 页码：1082-1091
- 文件大小：974 K
摘要
The purpose of this study was to identify the role of phospholipase D (PLD) isozymes in Bcl-2 expression. Overexpression of PLD1 or PLD2 increased Bcl-2 expression and phosphatidic acid (PA), the product of PLDs, also upregulated Bcl-2 expression. Treatment with PA activated the phospholipase A2 (PLA2)/Gi/ERK1/2, RhoA/Rho-associated kinase (ROCK)/p38 MAPK, and Rac1/p38 MAPK pathways. PA-induced phosphorylation of ERK1/2 was attenuated by a PLA2 inhibitor (mepacrine) and, a Gi protein inhibitor (pertussis toxin, PTX). On the other hand, p38 MAPK phosphorylation was attenuated by a dominant negative Rac1 and a specific Rho-kinase inhibitor (Y-27632). These results suggest that PLA2/Gi acts at the upstream of ERK1/2, while Rac1 and RhoA/ROCK act upstream of p38 MAPK. We next, tried to determine which transcription factor is involved in PLD-related Bcl-2 expression. When signal transducer and activator of transcription 3 (STAT3) activity was blocked by a STAT3 specific siRNA, PA-induced Bcl-2 expression was remarkably decreased, suggesting that STAT3 is an essential transcription factor linking PLD to Bcl-2 upregulation. Taken together, these findings indicate that PLD acts as an important regulator in Bcl-2 expression by activating STAT3 involving the phosphorylation of Ser727 through the PLA2/Gi/ERK1/2, RhoA/ROCK/p38 MAPK, and Rac1/p38 MAPK pathways.