alpha(1)-Adrenergic Receptor-Induced Cytoskeletal Organization and Cell Motility in CCL39 Fibroblasts Requires Phospholipase D1

作者：Wallert M; McCoy A; Voog J; Rastedt D; Taves Patterson J; Korpi Steiner N; Canine J; Ngyuen T; Nguyen C; Provost J^*

来源：Journal of Cellular Biochemistry, 2011, 112(10): 3025-3034.

DOI：10.1002/jcb.23227

• PHOSPHOLIPASE D
• PLD1
• PLD2
• STRESS FIBER
• CCL39 FIBROBLAST
• CELL MOTILITY
• RAS
• PROTEIN KINASE C ALPHA
• ALPHA ONE ADRENERGIC RECEPTOR
• PHENYLEPHRINE
• RHOA
• MAPK
• ERK
• RAF

The role of phospholipase D (PLD) in cytoskeletal reorganization, ERK activation, and migration is well established. Both isoforms of PLD (PLD1 and PLD2) can independently activate stress fiber formation and increase ERK phosphorylation. However, the isoform's specificity, upstream activators, and downstream targets of PLD that coordinate this process are less well understood. This study explores the role of alpha(1)-adrenergic receptor stimulation and its effect on PLD activity. We demonstrate that PLD1 activators, RhoA, and PKC alpha are critical for stress fiber formation and ERK activation, and enhance the production of phosphatidic acid (PA) upon phenylephrine addition. Ectopic expression of dominant negative PLD1 and not PLD2 blocks ERK activation, inhibits stress fiber formation, and reduces cell motility in CCL39 fibroblasts. Furthermore, we demonstrate the mechanism for PLD1 activation of ERK involves Ras. This work indicates that PLD1 plays a novel role mediating growth factor and cell motility events in a1-adrenergic receptor-activated cells. J. Cell. Biochem. 112: 3025-3034, 2011.

• 出版日期2011-10