Overexpression of phospholipase D enhances Bcl-2 expression by activating STAT3 through independent activation of ERK and p38MAPK in HeLa cells
- Title
- Overexpression of phospholipase D enhances Bcl-2 expression by activating STAT3 through independent activation of ERK and p38MAPK in HeLa cells
- Author
- 한중수
- Keywords
- Phospholipase D (PLD); Phosphatidic acid (PA); Bcl-2; MAPK; RhoA; STAT3 (ser727)
- Issue Date
- 2012-03
- Publisher
- Elsevier Science B.V., Amsterdam.
- Citation
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol.1823, No.6 [2012], p1082-1091
- Abstract
- 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.
- URI
- http://www.sciencedirect.com/science/article/pii/S016748891200081X?via%3Dihubhttp://hdl.handle.net/20.500.11754/67682
- ISSN
- 0006-3002
- DOI
- 10.1016/j.bbamcr.2012.03.015
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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